Insights into Early Recovery from Influenza Pneumonia by Spatial and Temporal Quantification of Putative Lung Regenerating Cells and by Lung Proteomics
Identifieur interne : 000935 ( Pmc/Curation ); précédent : 000934; suivant : 000936Insights into Early Recovery from Influenza Pneumonia by Spatial and Temporal Quantification of Putative Lung Regenerating Cells and by Lung Proteomics
Auteurs : Joe Wee Jian Ong [Singapour] ; Kai Sen Tan [Singapour] ; Siok Ghee Ler [Singapour] ; Jayantha Gunaratne [Singapour] ; Hyungwon Choi [Singapour] ; Ju Ee Seet [Singapour] ; Vincent Tak-Kwong Chow [Singapour]Source :
- Cells [ 2073-4409 ] ; 2019.
Abstract
During influenza pneumonia, the alveolar epithelial cells of the lungs are targeted by the influenza virus. The distal airway stem cells (DASCs) and proliferating alveolar type II (AT2) cells are reported to be putative lung repair cells. However, their relative spatial and temporal distribution is still unknown during influenza-induced acute lung injury. Here, we investigated the distribution of these cells, and concurrently performed global proteomic analysis of the infected lungs to elucidate and link the cellular and molecular events during influenza pneumonia recovery. BALB/c mice were infected with a sub-lethal dose of influenza H1N1 virus. From 5 to 25 days post-infection (dpi), mouse lungs were subjected to histopathologic and immunofluorescence analysis to probe for global distribution of lung repair cells (using P63 and KRT5 markers for DASCs; SPC and PCNA markers for AT2 cells). At 7 and 15 dpi, infected mouse lungs were also subjected to protein mass spectrometry for relative protein quantification. DASCs appeared only in the damaged area of the lung from 7 dpi onwards, reaching a peak at 21 dpi, and persisted until 25 dpi. However, no differentiation of DASCs to AT2 cells was observed by 25 dpi. In contrast, AT2 cells began proliferating from 7 dpi to replenish their population, especially within the boundary area between damaged and undamaged areas of the infected lungs. Mass spectrometry and gene ontology analysis revealed prominent innate immune responses at 7 dpi, which shifted towards adaptive immune responses by 15 dpi. Hence, proliferating AT2 cells but not DASCs contribute to AT2 cell regeneration following transition from innate to adaptive immune responses during the early phase of recovery from influenza pneumonia up to 25 dpi.
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DOI: 10.3390/cells8090975
PubMed: 31455003
PubMed Central: 6769472
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id="af1-cells-08-00975">Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545</wicri:regionArea></affiliation></author><author><name sortKey="Tan, Kai Sen" sort="Tan, Kai Sen" uniqKey="Tan K" first="Kai Sen" last="Tan">Kai Sen Tan</name><affiliation wicri:level="1"><nlm:aff id="af2-cells-08-00975">Department of Otolaryngology, National University of Singapore, Singapore 119228, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Otolaryngology, National University of Singapore, Singapore 119228</wicri:regionArea></affiliation></author><author><name sortKey="Ler, Siok Ghee" sort="Ler, Siok Ghee" uniqKey="Ler S" first="Siok Ghee" last="Ler">Siok Ghee Ler</name><affiliation wicri:level="1"><nlm:aff id="af3-cells-08-00975">Institute of Molecular and Cell Biology, Singapore 138673, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Institute of Molecular and Cell Biology, Singapore 138673</wicri:regionArea></affiliation></author><author><name sortKey="Gunaratne, Jayantha" sort="Gunaratne, Jayantha" uniqKey="Gunaratne J" first="Jayantha" last="Gunaratne">Jayantha Gunaratne</name><affiliation wicri:level="1"><nlm:aff id="af3-cells-08-00975">Institute of Molecular and Cell Biology, Singapore 138673, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Institute of Molecular and Cell Biology, Singapore 138673</wicri:regionArea></affiliation></author><author><name sortKey="Choi, Hyungwon" sort="Choi, Hyungwon" uniqKey="Choi H" first="Hyungwon" last="Choi">Hyungwon Choi</name><affiliation wicri:level="1"><nlm:aff id="af3-cells-08-00975">Institute of Molecular and Cell Biology, Singapore 138673, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Institute of Molecular and Cell Biology, Singapore 138673</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-cells-08-00975">Department of Medicine, National University of Singapore, Singapore 117599, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Medicine, National University of Singapore, Singapore 117599</wicri:regionArea></affiliation></author><author><name sortKey="Seet, Ju Ee" sort="Seet, Ju Ee" uniqKey="Seet J" first="Ju Ee" last="Seet">Ju Ee Seet</name><affiliation wicri:level="1"><nlm:aff id="af5-cells-08-00975">Department of Pathology, National University of Singapore, Singapore 119074, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Pathology, National University of Singapore, Singapore 119074</wicri:regionArea></affiliation></author><author><name sortKey="Chow, Vincent Tak Kwong" sort="Chow, Vincent Tak Kwong" uniqKey="Chow V" first="Vincent Tak-Kwong" last="Chow">Vincent Tak-Kwong Chow</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-00975">Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cells</title><idno type="eISSN">2073-4409</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>During influenza pneumonia, the alveolar epithelial cells of the lungs are targeted by the influenza virus. The distal airway stem cells (DASCs) and proliferating alveolar type II (AT2) cells are reported to be putative lung repair cells. However, their relative spatial and temporal distribution is still unknown during influenza-induced acute lung injury. Here, we investigated the distribution of these cells, and concurrently performed global proteomic analysis of the infected lungs to elucidate and link the cellular and molecular events during influenza pneumonia recovery. BALB/c mice were infected with a sub-lethal dose of influenza H1N1 virus. From 5 to 25 days post-infection (dpi), mouse lungs were subjected to histopathologic and immunofluorescence analysis to probe for global distribution of lung repair cells (using P63 and KRT5 markers for DASCs; SPC and PCNA markers for AT2 cells). At 7 and 15 dpi, infected mouse lungs were also subjected to protein mass spectrometry for relative protein quantification. DASCs appeared only in the damaged area of the lung from 7 dpi onwards, reaching a peak at 21 dpi, and persisted until 25 dpi. However, no differentiation of DASCs to AT2 cells was observed by 25 dpi. In contrast, AT2 cells began proliferating from 7 dpi to replenish their population, especially within the boundary area between damaged and undamaged areas of the infected lungs. Mass spectrometry and gene ontology analysis revealed prominent innate immune responses at 7 dpi, which shifted towards adaptive immune responses by 15 dpi. Hence, proliferating AT2 cells but not DASCs contribute to AT2 cell regeneration following transition from innate to adaptive immune responses during the early phase of recovery from influenza pneumonia up to 25 dpi.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Van Der Vliet, A" uniqKey="Van Der Vliet A">A. Van der Vliet</name></author><author><name sortKey="Cross, C E" uniqKey="Cross C">C.E. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cells</journal-id><journal-id journal-id-type="iso-abbrev">Cells</journal-id><journal-id journal-id-type="publisher-id">cells</journal-id><journal-title-group><journal-title>Cells</journal-title></journal-title-group><issn pub-type="epub">2073-4409</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31455003</article-id><article-id pub-id-type="pmc">6769472</article-id><article-id pub-id-type="doi">10.3390/cells8090975</article-id><article-id pub-id-type="publisher-id">cells-08-00975</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Insights into Early Recovery from Influenza Pneumonia by Spatial and Temporal Quantification of Putative Lung Regenerating Cells and by Lung Proteomics</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-2634-6213</contrib-id><name><surname>Ong</surname><given-names>Joe Wee Jian</given-names></name><xref ref-type="aff" rid="af1-cells-08-00975">1</xref><xref rid="c1-cells-08-00975" ref-type="corresp">*</xref><xref ref-type="author-notes" rid="fn1-cells-08-00975">†</xref></contrib><contrib contrib-type="author"><name><surname>Tan</surname><given-names>Kai Sen</given-names></name><xref ref-type="aff" rid="af2-cells-08-00975">2</xref><xref ref-type="author-notes" rid="fn1-cells-08-00975">†</xref></contrib><contrib contrib-type="author"><name><surname>Ler</surname><given-names>Siok Ghee</given-names></name><xref ref-type="aff" rid="af3-cells-08-00975">3</xref></contrib><contrib contrib-type="author"><name><surname>Gunaratne</surname><given-names>Jayantha</given-names></name><xref ref-type="aff" rid="af3-cells-08-00975">3</xref></contrib><contrib contrib-type="author"><name><surname>Choi</surname><given-names>Hyungwon</given-names></name><xref ref-type="aff" rid="af3-cells-08-00975">3</xref><xref ref-type="aff" rid="af4-cells-08-00975">4</xref></contrib><contrib contrib-type="author"><name><surname>Seet</surname><given-names>Ju Ee</given-names></name><xref ref-type="aff" rid="af5-cells-08-00975">5</xref></contrib><contrib contrib-type="author"><name><surname>Chow</surname><given-names>Vincent Tak-Kwong</given-names></name><xref ref-type="aff" rid="af1-cells-08-00975">1</xref><xref rid="c1-cells-08-00975" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-cells-08-00975"><label>1</label>Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore</aff><aff id="af2-cells-08-00975"><label>2</label>Department of Otolaryngology, National University of Singapore, Singapore 119228, Singapore</aff><aff id="af3-cells-08-00975"><label>3</label>Institute of Molecular and Cell Biology, Singapore 138673, Singapore</aff><aff id="af4-cells-08-00975"><label>4</label>Department of Medicine, National University of Singapore, Singapore 117599, Singapore</aff><aff id="af5-cells-08-00975"><label>5</label>Department of Pathology, National University of Singapore, Singapore 119074, Singapore</aff><author-notes><corresp id="c1-cells-08-00975"><label>*</label>Correspondence: <email>micowjj@nus.edu.sg</email> (J.W.J.O.); <email>micctk@nus.edu.sg</email> (V.T.-K.C.); Tel.: +65-6516-3691 (J.W.J.O.)</corresp><fn id="fn1-cells-08-00975"><label>†</label><p>These authors contributed equally.</p></fn></author-notes><pub-date pub-type="epub"><day>26</day><month>8</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>9</month><year>2019</year></pub-date><volume>8</volume><issue>9</issue><elocation-id>975</elocation-id><history><date date-type="received"><day>31</day><month>5</month><year>2019</year></date><date date-type="accepted"><day>21</day><month>8</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>During influenza pneumonia, the alveolar epithelial cells of the lungs are targeted by the influenza virus. The distal airway stem cells (DASCs) and proliferating alveolar type II (AT2) cells are reported to be putative lung repair cells. However, their relative spatial and temporal distribution is still unknown during influenza-induced acute lung injury. Here, we investigated the distribution of these cells, and concurrently performed global proteomic analysis of the infected lungs to elucidate and link the cellular and molecular events during influenza pneumonia recovery. BALB/c mice were infected with a sub-lethal dose of influenza H1N1 virus. From 5 to 25 days post-infection (dpi), mouse lungs were subjected to histopathologic and immunofluorescence analysis to probe for global distribution of lung repair cells (using P63 and KRT5 markers for DASCs; SPC and PCNA markers for AT2 cells). At 7 and 15 dpi, infected mouse lungs were also subjected to protein mass spectrometry for relative protein quantification. DASCs appeared only in the damaged area of the lung from 7 dpi onwards, reaching a peak at 21 dpi, and persisted until 25 dpi. However, no differentiation of DASCs to AT2 cells was observed by 25 dpi. In contrast, AT2 cells began proliferating from 7 dpi to replenish their population, especially within the boundary area between damaged and undamaged areas of the infected lungs. Mass spectrometry and gene ontology analysis revealed prominent innate immune responses at 7 dpi, which shifted towards adaptive immune responses by 15 dpi. Hence, proliferating AT2 cells but not DASCs contribute to AT2 cell regeneration following transition from innate to adaptive immune responses during the early phase of recovery from influenza pneumonia up to 25 dpi.</p></abstract><kwd-group><kwd>influenza</kwd><kwd>pneumonia</kwd><kwd>lung regeneration</kwd><kwd>stem cells</kwd><kwd>comparative quantification</kwd><kwd>P63</kwd><kwd>KRT5</kwd><kwd>proliferating alveolar type II cells</kwd><kwd>proteomics</kwd></kwd-group></article-meta></front><floats-group><fig id="cells-08-00975-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Histopathology and corresponding immunofluorescence staining for P63 and KRT5 within infected mouse lungs over a period until 25 dpi. The top row shows representative H&E images of infected mouse lungs at various time-points following infection. The middle row depicts the zoomed-in images of the top row, while the bottom row portrays the corresponding immunofluorescence staining for P63 and KRT5. No P63-KRT5-positive cells were detected in control uninfected mouse lungs (<bold>A</bold>). DASCs first appeared as small peribronchiolar pods at 9 dpi, before radiating outwards as distinct KRT5-positive pods (<bold>B</bold>–<bold>E</bold>). Formation of lumens was observed by 13 dpi (<bold>F</bold>). DASCs were observed to flatten out and to line the new lumens by 19 dpi (<bold>G</bold>–<bold>I</bold>), and this trend persisted until 25 dpi (<bold>J</bold>–<bold>L</bold>; summarized in <xref rid="cells-08-00975-t001" ref-type="table">Table 1</xref>).</p></caption><graphic xlink:href="cells-08-00975-g001a"></graphic><graphic xlink:href="cells-08-00975-g001b"></graphic></fig><fig id="cells-08-00975-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>DASCs do not express SPC, the alveolar type II epithelial cell marker. At all three time-points of 13, 19 and 25 dpi, DASCs did not express SPC, suggesting the absence of the differentiation process (<bold>A</bold>–<bold>F</bold>), quantified in (<bold>G</bold>). Some SPC (red) immunofluorescence signal was detected at 25 dpi (<bold>C</bold>), but this was background staining since it appeared in the bronchiolar air-spaces. Decreased proliferation of the DASCs was also observed from 13 to 25 dpi, based on the intensity of PCNA staining (<bold>D</bold>–<bold>F</bold>). To serve as a control, the undamaged area of lungs at 25 dpi expressed SPC, but did not express P63, KRT5 and PCNA (<bold>H</bold>).</p></caption><graphic xlink:href="cells-08-00975-g002"></graphic></fig><fig id="cells-08-00975-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Spatial and temporal quantification of proliferating AT2 cells reveal significant trends during recovery from influenza pneumonia. The number of proliferating for both BA and UA, the peak number of proliferating cells was significantly higher in the BA (<bold>A</bold>,<bold>B</bold>,<bold>D</bold>,<bold>E</bold>). Proliferating AT2 cells in the damaged area (DA) increased from 13 dpi, and peaked at 19 dpi (<bold>G</bold>,<bold>H</bold>). From 21 to 25 dpi, the number of these cells in DA remained higher than BA and UA, whose numbers had diminished to less than 10 cells per field (<bold>A</bold>,<bold>D</bold>,<bold>G</bold>). AT2 cell numbers exhibited an increasing trend from 15 to 25 dpi for BA (<bold>C</bold>), UA (<bold>F</bold>) and DA (<bold>I</bold>), suggesting the AT2 cells were being replenished through AT2 proliferation. * indicates <italic>p</italic> < 0.05, *** indicates <italic>p</italic> < 0.001, **** indicates <italic>p</italic> < 0.0001, # indicates <italic>p</italic> < 0.1. Statistical analysis was conducted by Student’s <italic>t</italic>-test, comparing the cell number of each time-point of each area against that of the respective area at 5 dpi. Error bars were calculated as the standard deviation from three different mice per time-point (5 fields per mouse lung).</p></caption><graphic xlink:href="cells-08-00975-g003"></graphic></fig><fig id="cells-08-00975-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Major up- and down-regulated proteins in whole infected mouse lungs at 7 and 15 dpi. At 7 dpi (<bold>A</bold>), the top 5 out of 271 up-regulated proteins were IFI44, IIGP1, IFIT1, APCS and HP, which are mainly related to innate immunity. The top 5 out of 336 down-regulated proteins were CBR2, COL1A1, SFTPA1, LAMC2, and SFTPB, implying alveolar epithelial damage. At 15 dpi (<bold>B</bold>), the top 5 out of 298 up-regulated proteins were IGH-1A, IGH-3, IFI44, TNC and TAPBP, suggesting the transition to the adaptive immune response. The top 5 out of 393 down-regulated proteins were CBR2, TPPP3, CBR2, MB and PVALB, reflecting persistent damage in the lungs. The functions of the proteins are summarized in <xref rid="cells-08-00975-t002" ref-type="table">Table 2</xref>. Proteins coded in black depict non-significant proteins (FDR > 0.01, and number of peptides < 5). The fold change in the expression of each protein is relative to that of control uninfected mice.</p></caption><graphic xlink:href="cells-08-00975-g004"></graphic></fig><table-wrap id="cells-08-00975-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">cells-08-00975-t001_Table 1</object-id><label>Table 1</label><caption><p>Histology and KRT5 expression of infected mouse lungs over time.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Day</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Histology Description</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">KRT5 Expression</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">5</td><td align="center" valign="middle" rowspan="1" colspan="1">No recovery.</td><td align="center" valign="middle" rowspan="1" colspan="1">No KRT5+ cells.</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">7</td><td align="center" valign="middle" rowspan="1" colspan="1">No recovery.</td><td align="center" valign="middle" rowspan="1" colspan="1">KRT5+ cells at bronchioles.</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">9</td><td align="center" valign="middle" rowspan="1" colspan="1">Small pods <sup>1</sup> seen adjacent to bronchioles.</td><td align="center" valign="middle" rowspan="1" colspan="1">Small KRT5+ pods near bronchioles.</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">Epithelial regeneration seen as obvious pods as well as single cells radiating out from airway.</td><td align="center" valign="middle" rowspan="1" colspan="1">Obvious KRT5+ pods.</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">13</td><td align="center" valign="middle" rowspan="1" colspan="1">Epithelial regeneration seen as mainly pods with formation of a few lumens.</td><td align="center" valign="middle" rowspan="1" colspan="1">Obvious KRT5+ pods.</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">15</td><td align="center" valign="middle" rowspan="1" colspan="1">Epithelial regeneration seen in all damaged alveoli. Most of the pods were beginning to show lumens.</td><td align="center" valign="middle" rowspan="1" colspan="1">Obvious KRT5+ pods.</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">17</td><td align="center" valign="middle" rowspan="1" colspan="1">Similar to 15 dpi. More pods showing lumens.</td><td align="center" valign="middle" rowspan="1" colspan="1">KRT5 expression still strong.</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">19</td><td align="center" valign="middle" rowspan="1" colspan="1">Lumens began to flatten out and to line alveolar spaces.</td><td align="center" valign="middle" rowspan="1" colspan="1">KRT5 expression still strong.</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">21</td><td align="center" valign="middle" rowspan="1" colspan="1">Progression from 19 dpi.</td><td align="center" valign="middle" rowspan="1" colspan="1">KRT5 staining intensity reducing.</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">23</td><td align="center" valign="middle" rowspan="1" colspan="1">Progression from 21 dpi.</td><td align="center" valign="middle" rowspan="1" colspan="1">KRT5 staining faint.</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">25</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Progression from 23 dpi.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">KRT5 staining even fainter.</td></tr></tbody></table><table-wrap-foot><fn><p><sup>1</sup> Pods are defined as compact groups of DASCs expressing KRT5 and/or P63 and without a lumen.</p></fn></table-wrap-foot></table-wrap><table-wrap id="cells-08-00975-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">cells-08-00975-t002_Table 2</object-id><label>Table 2</label><caption><p>Functions of major up- and down-regulated proteins at 7 and 15 dpi.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Day</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Regulation</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Gene</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Function</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">7 dpi</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">15 dpi</th></tr></thead><tbody><tr><td rowspan="5" align="center" valign="middle" style="border-bottom:solid thin" colspan="1"><bold>7</bold></td><td rowspan="5" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Up</td><td align="center" valign="middle" rowspan="1" colspan="1">IFI44</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Interferon alpha induced protein</bold>. Anti-proliferative activity [<xref rid="B36-cells-08-00975" ref-type="bibr">36</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">+29.4</td><td align="center" valign="middle" rowspan="1" colspan="1">+9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">IIGP1</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Interferon inducible GTPase 1</bold>. Contributes to resistance against intracellular pathogen [<xref rid="B37-cells-08-00975" ref-type="bibr">37</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">+9.3</td><td align="center" valign="middle" rowspan="1" colspan="1">+6.4</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">IFIT1</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Interferon inducible antiviral RNA-binding protein</bold>. Antiviral activity against influenza virus [<xref rid="B38-cells-08-00975" ref-type="bibr">38</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">+7.2</td><td align="center" valign="middle" rowspan="1" colspan="1">+2.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">APCS</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Serum amyloid P-component</bold>. Acute phase protein [<xref rid="B39-cells-08-00975" ref-type="bibr">39</xref>,<xref rid="B40-cells-08-00975" ref-type="bibr">40</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">+7.2</td><td align="center" valign="middle" rowspan="1" colspan="1">+3.5</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HP</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Haptoglobin</bold>. Acute phase protein [<xref rid="B41-cells-08-00975" ref-type="bibr">41</xref>].</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+7.1</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">N.D.</td></tr><tr><td rowspan="5" align="center" valign="middle" style="border-bottom:solid thin" colspan="1"><bold>7</bold></td><td rowspan="5" align="center" valign="middle" style="border-bottom:solid thin" colspan="1"><bold>Down</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">CBR2</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Carbonyl reductase</bold>. Involved in pulmonary metabolism and highly expressed in alveolar type II cells [<xref rid="B42-cells-08-00975" ref-type="bibr">42</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">−3.4</td><td align="center" valign="middle" rowspan="1" colspan="1">−8.7</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">COL1A1</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Collagen alpha-1(I) chain</bold>, part of type I collagen. Part of lung extracellular matrix [<xref rid="B43-cells-08-00975" ref-type="bibr">43</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">−3.1</td><td align="center" valign="middle" rowspan="1" colspan="1">−1.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">SFTPA1</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Surfactant protein A1</bold>. Marker of alveolar type II cells.</td><td align="center" valign="middle" rowspan="1" colspan="1">−2.9</td><td align="center" valign="middle" rowspan="1" colspan="1">−2.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">LAMC2</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Laminin subunit gamma-2</bold>. Subunit of laminin, essential for adherence of epithelial cells to basal membrane [<xref rid="B44-cells-08-00975" ref-type="bibr">44</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">−2.9</td><td align="center" valign="middle" rowspan="1" colspan="1">N.D.</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SFTPB</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Surfactant protein B.</bold> Marker of alveolar type II cells.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">−2.8</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">−1.6</td></tr><tr><td rowspan="5" align="center" valign="middle" style="border-bottom:solid thin" colspan="1"><bold>15</bold></td><td rowspan="5" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Up</td><td align="center" valign="middle" rowspan="1" colspan="1">IGH-1A</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Immunoglobulin gamma 2A chain C region.</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">+4.7</td><td align="center" valign="middle" rowspan="1" colspan="1">+28.2</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">IGH-3</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Immunoglobulin gamma 2B chain C region.</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">+3.5</td><td align="center" valign="middle" rowspan="1" colspan="1">+9.5</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">IFI44</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Interferon alpha induced protein</bold>. Anti-proliferative activity [<xref rid="B36-cells-08-00975" ref-type="bibr">36</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">+29.4</td><td align="center" valign="middle" rowspan="1" colspan="1">+9.0</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">TNC</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Tenascin C</bold>. Implicated in fibrosis persistence [<xref rid="B30-cells-08-00975" ref-type="bibr">30</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">+2.2</td><td align="center" valign="middle" rowspan="1" colspan="1">+9.0</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">TAPBP</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Tapasin</bold>. Essential for MHC Class I-TAP complex synthesis [<xref rid="B31-cells-08-00975" ref-type="bibr">31</xref>]. Lowly expressed in stem cells [<xref rid="B32-cells-08-00975" ref-type="bibr">32</xref>,<xref rid="B33-cells-08-00975" ref-type="bibr">33</xref>].</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+6.4</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+6.5</td></tr><tr><td rowspan="5" align="center" valign="middle" style="border-bottom:solid thin" colspan="1"><bold>15</bold></td><td rowspan="5" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Down</td><td align="center" valign="middle" rowspan="1" colspan="1">CBR2</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Carbonyl reductase</bold>. Involved in pulmonary metabolism and highly expressed in alveolar type II cells [<xref rid="B42-cells-08-00975" ref-type="bibr">42</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">−3.4</td><td align="center" valign="middle" rowspan="1" colspan="1">−8.7</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">TPPP3</td><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Tubulin polymerization promoting protein</bold>. Associated with proliferation [<xref rid="B34-cells-08-00975" ref-type="bibr">34</xref>].</td><td align="center" valign="middle" rowspan="1" colspan="1">−2.7</td><td align="center" valign="middle" rowspan="1" colspan="1">−7.1</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">MB</td><td rowspan="2" align="center" valign="middle" colspan="1"><bold>Myoglobin</bold> and <bold>parvalbumin</bold>. Associated with muscles.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.D.</td><td align="center" valign="middle" rowspan="1" colspan="1">−5.2</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">PVALB</td><td align="center" valign="middle" rowspan="1" colspan="1">N.D.</td><td align="center" valign="middle" rowspan="1" colspan="1">−4.8</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SDPR</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Caveolae-associated protein 2</bold>. Associated with angiogenesis by regulating eNOS activity [<xref rid="B35-cells-08-00975" ref-type="bibr">35</xref>].</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">−2.4</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">−4.5</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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