Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract
Identifieur interne : 001097 ( Main/Exploration ); précédent : 001096; suivant : 001098Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract
Auteurs : David K. Meyerholz [États-Unis] ; Allyn M. Lambertz [États-Unis] ; Paul B. Mccray [États-Unis]Source :
- The American Journal of Pathology [ 0002-9440 ] ; 2015.
Abstract
Dipeptidyl peptidase 4 (DPP4, CD26), a type II transmembrane ectopeptidase, is the receptor for the Middle Eastern respiratory syndrome coronavirus (MERS-CoV). MERS emerged in 2012 and has a high mortality associated with severe lung disease. A lack of autopsy studies from MERS fatalities has hindered understanding of MERS-CoV pathogenesis. We investigated the spatial and cellular localization of DPP4 to evaluate an association MERS clinical disease. DPP4 was rarely detected in the surface epithelium from nasal cavity to conducting airways with a slightly increased incidence in distal airways. DPP4 was also found in a subset of mononuclear leukocytes and in serous cells of submucosal glands. In the parenchyma, DPP4 was found principally in type I and II cells and alveolar macrophages and was also detected in vascular endothelium (eg, lymphatics) and pleural mesothelia. Patients with chronic lung disease, such as chronic obstructive pulmonary disease and cystic fibrosis, exhibited increased DPP4 immunostaining in alveolar epithelia (type I and II cells) and alveolar macrophages with similar trends in reactive mesothelia. This finding suggests that preexisting pulmonary disease could increase MERS-CoV receptor abundance and predispose individuals to MERS morbidity and mortality, which is consistent with current clinical observations. We speculate that the preferential spatial localization of DPP4 in alveolar regions may explain why MERS is characterized by lower respiratory tract disease.
Url:
DOI: 10.1016/j.ajpath.2015.09.014
PubMed: 26597880
PubMed Central: 4715219
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract</title><author><name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Lambertz, Allyn M" sort="Lambertz, Allyn M" uniqKey="Lambertz A" first="Allyn M." last="Lambertz">Allyn M. Lambertz</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B." last="Mccray">Paul B. Mccray</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26597880</idno><idno type="pmc">4715219</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715219</idno><idno type="RBID">PMC:4715219</idno><idno type="doi">10.1016/j.ajpath.2015.09.014</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000799</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000799</idno><idno type="wicri:Area/Pmc/Curation">000799</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000799</idno><idno type="wicri:Area/Pmc/Checkpoint">000579</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000579</idno><idno type="wicri:Area/Ncbi/Merge">000573</idno><idno type="wicri:Area/Ncbi/Curation">000573</idno><idno type="wicri:Area/Ncbi/Checkpoint">000573</idno><idno type="wicri:doubleKey">0002-9440:2015:Meyerholz D:dipeptidyl:peptidase:distribution</idno><idno type="wicri:Area/Main/Merge">001099</idno><idno type="wicri:Area/Main/Curation">001097</idno><idno type="wicri:Area/Main/Exploration">001097</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract</title><author><name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Lambertz, Allyn M" sort="Lambertz, Allyn M" uniqKey="Lambertz A" first="Allyn M." last="Lambertz">Allyn M. Lambertz</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B." last="Mccray">Paul B. Mccray</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City</wicri:cityArea></affiliation></author></analytic><series><title level="j">The American Journal of Pathology</title><idno type="ISSN">0002-9440</idno><idno type="eISSN">1525-2191</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Dipeptidyl peptidase 4 (DPP4, CD26), a type II transmembrane ectopeptidase, is the receptor for the Middle Eastern respiratory syndrome coronavirus (MERS-CoV). MERS emerged in 2012 and has a high mortality associated with severe lung disease. A lack of autopsy studies from MERS fatalities has hindered understanding of MERS-CoV pathogenesis. We investigated the spatial and cellular localization of DPP4 to evaluate an association MERS clinical disease. DPP4 was rarely detected in the surface epithelium from nasal cavity to conducting airways with a slightly increased incidence in distal airways. DPP4 was also found in a subset of mononuclear leukocytes and in serous cells of submucosal glands. In the parenchyma, DPP4 was found principally in type I and II cells and alveolar macrophages and was also detected in vascular endothelium (eg, lymphatics) and pleural mesothelia. Patients with chronic lung disease, such as chronic obstructive pulmonary disease and cystic fibrosis, exhibited increased DPP4 immunostaining in alveolar epithelia (type I and II cells) and alveolar macrophages with similar trends in reactive mesothelia. This finding suggests that preexisting pulmonary disease could increase MERS-CoV receptor abundance and predispose individuals to MERS morbidity and mortality, which is consistent with current clinical observations. We speculate that the preferential spatial localization of DPP4 in alveolar regions may explain why MERS is characterized by lower respiratory tract disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T.M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A.D. Osterhaus</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R.A. 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Pohlmann</name></author><author><name sortKey="Mckerrow, J H" uniqKey="Mckerrow J">J.H. McKerrow</name></author><author><name sortKey="Renslo, A R" uniqKey="Renslo A">A.R. Renslo</name></author><author><name sortKey="Simmons, G" uniqKey="Simmons G">G. Simmons</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Iowa</li></region></list><tree><country name="États-Unis"><region name="Iowa"><name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name></region><name sortKey="Lambertz, Allyn M" sort="Lambertz, Allyn M" uniqKey="Lambertz A" first="Allyn M." last="Lambertz">Allyn M. Lambertz</name><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B." last="Mccray">Paul B. Mccray</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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