Lymphangiogenesis and lymphatic remodeling induced by filarial parasites: implications for pathogenesis.
Identifieur interne : 002C42 ( PubMed/Corpus ); précédent : 002C41; suivant : 002C43Lymphangiogenesis and lymphatic remodeling induced by filarial parasites: implications for pathogenesis.
Auteurs : Sasisekhar Bennuru ; Thomas B. NutmanSource :
- PLoS pathogens [ 1553-7374 ] ; 2009.
English descriptors
- KwdEn :
- Cell Differentiation (immunology), Cell Proliferation, Cell Separation, Elephantiasis, Filarial (genetics), Elephantiasis, Filarial (immunology), Elephantiasis, Filarial (pathology), Endothelial Cells (immunology), Endothelial Cells (parasitology), Endothelial Cells (pathology), Flow Cytometry, Gene Expression (immunology), Humans, Lymphangiogenesis (immunology), Matrix Metalloproteinase 1 (biosynthesis), Matrix Metalloproteinase 1 (immunology), Matrix Metalloproteinase 2 (biosynthesis), Matrix Metalloproteinase 2 (immunology), Microscopy, Confocal, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Tissue Inhibitor of Metalloproteinase-1 (biosynthesis), Tissue Inhibitor of Metalloproteinase-1 (immunology), Tissue Inhibitor of Metalloproteinase-2 (biosynthesis), Tissue Inhibitor of Metalloproteinase-2 (immunology).
- MESH :
- chemical , biosynthesis : Matrix Metalloproteinase 1, Matrix Metalloproteinase 2, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2.
- genetics : Elephantiasis, Filarial.
- immunology : Cell Differentiation, Elephantiasis, Filarial, Endothelial Cells, Gene Expression, Lymphangiogenesis, Matrix Metalloproteinase 1, Matrix Metalloproteinase 2, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2.
- parasitology : Endothelial Cells.
- pathology : Elephantiasis, Filarial, Endothelial Cells.
- Cell Proliferation, Cell Separation, Flow Cytometry, Humans, Microscopy, Confocal, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction.
Abstract
Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures in vitro. Moreover, serum from patently infected (microfilaria positive) patients and those with longstanding chronic lymphatic obstruction induced significantly increased LEC proliferation compared to sera from uninfected individuals. Differentiation of LEC into tube-like networks was found to be associated with significantly increased levels of matrix metalloproteases and inhibition of their TIMP inhibitors (Tissue inhibitors of matrix metalloproteases). Comparison of global gene expression induced by live parasites in LEC to parasite-unexposed LEC demonstrated that filarial parasites altered the expression of those genes involved in cellular organization and development as well as those associated with junction adherence pathways that in turn decreased trans-endothelial transport as assessed by FITC-Dextran. The data suggest that filarial parasites directly induce lymphangiogenesis and lymphatic differentiation and provide insight into the mechanisms underlying the pathology seen in lymphatic filariasis.
DOI: 10.1371/journal.ppat.1000688
PubMed: 20011114
Links to Exploration step
pubmed:20011114Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Lymphangiogenesis and lymphatic remodeling induced by filarial parasites: implications for pathogenesis.</title><author><name sortKey="Bennuru, Sasisekhar" sort="Bennuru, Sasisekhar" uniqKey="Bennuru S" first="Sasisekhar" last="Bennuru">Sasisekhar Bennuru</name><affiliation><nlm:affiliation>Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. bennurus@niaid.nih.gov</nlm:affiliation></affiliation></author><author><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B" last="Nutman">Thomas B. Nutman</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2009">2009</date><idno type="RBID">pubmed:20011114</idno><idno type="pmid">20011114</idno><idno type="doi">10.1371/journal.ppat.1000688</idno><idno type="wicri:Area/PubMed/Corpus">002C42</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002C42</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Lymphangiogenesis and lymphatic remodeling induced by filarial parasites: implications for pathogenesis.</title><author><name sortKey="Bennuru, Sasisekhar" sort="Bennuru, Sasisekhar" uniqKey="Bennuru S" first="Sasisekhar" last="Bennuru">Sasisekhar Bennuru</name><affiliation><nlm:affiliation>Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. bennurus@niaid.nih.gov</nlm:affiliation></affiliation></author><author><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B" last="Nutman">Thomas B. Nutman</name></author></analytic><series><title level="j">PLoS pathogens</title><idno type="eISSN">1553-7374</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Differentiation (immunology)</term><term>Cell Proliferation</term><term>Cell Separation</term><term>Elephantiasis, Filarial (genetics)</term><term>Elephantiasis, Filarial (immunology)</term><term>Elephantiasis, Filarial (pathology)</term><term>Endothelial Cells (immunology)</term><term>Endothelial Cells (parasitology)</term><term>Endothelial Cells (pathology)</term><term>Flow Cytometry</term><term>Gene Expression (immunology)</term><term>Humans</term><term>Lymphangiogenesis (immunology)</term><term>Matrix Metalloproteinase 1 (biosynthesis)</term><term>Matrix Metalloproteinase 1 (immunology)</term><term>Matrix Metalloproteinase 2 (biosynthesis)</term><term>Matrix Metalloproteinase 2 (immunology)</term><term>Microscopy, Confocal</term><term>Oligonucleotide Array Sequence Analysis</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Tissue Inhibitor of Metalloproteinase-1 (biosynthesis)</term><term>Tissue Inhibitor of Metalloproteinase-1 (immunology)</term><term>Tissue Inhibitor of Metalloproteinase-2 (biosynthesis)</term><term>Tissue Inhibitor of Metalloproteinase-2 (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Matrix Metalloproteinase 1</term><term>Matrix Metalloproteinase 2</term><term>Tissue Inhibitor of Metalloproteinase-1</term><term>Tissue Inhibitor of Metalloproteinase-2</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cell Differentiation</term><term>Elephantiasis, Filarial</term><term>Endothelial Cells</term><term>Gene Expression</term><term>Lymphangiogenesis</term><term>Matrix Metalloproteinase 1</term><term>Matrix Metalloproteinase 2</term><term>Tissue Inhibitor of Metalloproteinase-1</term><term>Tissue Inhibitor of Metalloproteinase-2</term></keywords><keywords scheme="MESH" qualifier="parasitology" xml:lang="en"><term>Endothelial Cells</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Elephantiasis, Filarial</term><term>Endothelial Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Proliferation</term><term>Cell Separation</term><term>Flow Cytometry</term><term>Humans</term><term>Microscopy, Confocal</term><term>Oligonucleotide Array Sequence Analysis</term><term>Reverse Transcriptase Polymerase Chain Reaction</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures in vitro. Moreover, serum from patently infected (microfilaria positive) patients and those with longstanding chronic lymphatic obstruction induced significantly increased LEC proliferation compared to sera from uninfected individuals. Differentiation of LEC into tube-like networks was found to be associated with significantly increased levels of matrix metalloproteases and inhibition of their TIMP inhibitors (Tissue inhibitors of matrix metalloproteases). Comparison of global gene expression induced by live parasites in LEC to parasite-unexposed LEC demonstrated that filarial parasites altered the expression of those genes involved in cellular organization and development as well as those associated with junction adherence pathways that in turn decreased trans-endothelial transport as assessed by FITC-Dextran. The data suggest that filarial parasites directly induce lymphangiogenesis and lymphatic differentiation and provide insight into the mechanisms underlying the pathology seen in lymphatic filariasis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20011114</PMID><DateCreated><Year>2009</Year><Month>12</Month><Day>17</Day></DateCreated><DateCompleted><Year>2010</Year><Month>02</Month><Day>24</Day></DateCompleted><DateRevised><Year>2016</Year><Month>10</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1553-7374</ISSN><JournalIssue CitedMedium="Internet"><Volume>5</Volume><Issue>12</Issue><PubDate><Year>2009</Year><Month>Dec</Month></PubDate></JournalIssue><Title>PLoS pathogens</Title><ISOAbbreviation>PLoS Pathog.</ISOAbbreviation></Journal><ArticleTitle>Lymphangiogenesis and lymphatic remodeling induced by filarial parasites: implications for pathogenesis.</ArticleTitle><Pagination><MedlinePgn>e1000688</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.ppat.1000688</ELocationID><Abstract><AbstractText>Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures in vitro. Moreover, serum from patently infected (microfilaria positive) patients and those with longstanding chronic lymphatic obstruction induced significantly increased LEC proliferation compared to sera from uninfected individuals. Differentiation of LEC into tube-like networks was found to be associated with significantly increased levels of matrix metalloproteases and inhibition of their TIMP inhibitors (Tissue inhibitors of matrix metalloproteases). Comparison of global gene expression induced by live parasites in LEC to parasite-unexposed LEC demonstrated that filarial parasites altered the expression of those genes involved in cellular organization and development as well as those associated with junction adherence pathways that in turn decreased trans-endothelial transport as assessed by FITC-Dextran. The data suggest that filarial parasites directly induce lymphangiogenesis and lymphatic differentiation and provide insight into the mechanisms underlying the pathology seen in lymphatic filariasis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bennuru</LastName><ForeName>Sasisekhar</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. bennurus@niaid.nih.gov</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nutman</LastName><ForeName>Thomas B</ForeName><Initials>TB</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Agency>Intramural NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>12</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS Pathog</MedlineTA><NlmUniqueID>101238921</NlmUniqueID><ISSNLinking>1553-7366</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019715">Tissue Inhibitor of Metalloproteinase-1</NameOfSubstance></Chemical><Chemical><RegistryNumber>127497-59-0</RegistryNumber><NameOfSubstance UI="D019716">Tissue Inhibitor of Metalloproteinase-2</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.24.24</RegistryNumber><NameOfSubstance UI="D020778">Matrix Metalloproteinase 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.24.7</RegistryNumber><NameOfSubstance UI="D020781">Matrix Metalloproteinase 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MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020781" MajorTopicYN="N">Matrix Metalloproteinase 1</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020778" MajorTopicYN="N">Matrix Metalloproteinase 2</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018613" MajorTopicYN="N">Microscopy, Confocal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020411" MajorTopicYN="N">Oligonucleotide Array Sequence Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020133" MajorTopicYN="N">Reverse Transcriptase Polymerase Chain Reaction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019715" 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