Journal article
Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract: Implications for the Middle East Respiratory Syndrome
The American journal of pathology, Vol.186(1), pp.78-86
01/2016
DOI: 10.1016/j.ajpath.2015.09.014
PMCID: PMC4715219
PMID: 26597880
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.
Details
- Title: Subtitle
- Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract: Implications for the Middle East Respiratory Syndrome
- Creators
- David K Meyerholz - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IowaAllyn M Lambertz - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IowaPaul B McCray Jr - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa. Electronic address: paul-mccray@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.186(1), pp.78-86
- DOI
- 10.1016/j.ajpath.2015.09.014
- PMID
- 26597880
- PMCID
- PMC4715219
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Grant note
- P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS P01 HL-091842 / NHLBI NIH HHS P01 HL-51670 / NHLBI NIH HHS P01 AI-060699 / NIAID NIH HHS P01 HL051670 / NHLBI NIH HHS P01 AI060699 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 01/2016
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Internal Medicine
- Record Identifier
- 9984083281302771
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