title: Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma.
abstract: The presence of the complement-derived anaphylatoxin peptides, C3a and C5a, in the lung can induce respiratory distress characterized by contraction of the smooth muscle walls in bronchioles and pulmonary arteries and aggregation of platelets and leukocytes in pulmonary vessels. C3a and C5a mediate these effects by binding to their specific receptors, C3aR and C5aR, respectively. The cells that express these receptors in the lung have not been thoroughly investigated, nor has their expression been examined during inflammation. Accordingly, C3aR and C5aR expression in normal human and murine lung was determined in this study by immunohistochemistry and in situ hybridization. In addition, the expression of these receptors was delineated in mice subjected to LPS- and OVA-induced models of inflammation. Under noninflamed conditions, C3aR and C5aR protein and mRNA were expressed by bronchial epithelial and smooth muscle cells of both human and mouse lung. C3aR expression increased significantly on both bronchial epithelial and smooth muscle cells in mice treated with LPS; however, in the OVA-challenged animals only the bronchial smooth muscle cells showed increased C3aR expression. C5aR expression also increased significantly on bronchial epithelial cells in mice treated with LPS, but was not elevated in either cell type in the OVA-challenged mice. These results demonstrate the expression of C3aR and C5aR by cells endogenous to the lung, and, given the participation of bronchial epithelial and smooth muscle cells in the pathology of diseases such as sepsis and asthma, the data suggest a role for these receptors during lung inflammation.
authors.affiliation: University of Texas-Houston Institute of Molecular Medicine for the Prevention of Human Diseases, and Department of Biochemistry and Molecular Biology, Houston, TX 77030, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Drouin
authors.forename: J
authors.initials: J
authors.lastname: Kildsgaard
authors.forename: J
authors.initials: J
authors.lastname: Haviland
authors.forename: J
authors.initials: J
authors.lastname: Zabner
authors.forename: H P
authors.initials: HP
authors.lastname: Jia
authors.forename: P B
authors.initials: PB
authors.lastname: McCray
authors.forename: B F
authors.initials: BF
authors.lastname: Tack
authors.forename: R A
authors.initials: RA
authors.lastname: Wetsel
mesh_terms: D000336:Aerosols; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000098:blood supply / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D015926:Complement C3a / Q000378:metabolism*; D015936:Complement C5a / Q000378:metabolism*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000096:biosynthesis* / Q000235:genetics; D020545:Respiratory Mucosa / Q000098:blood supply / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000336:Aerosols; D015703:Antigens, CD; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor; D015926:Complement C3a; D015936:Complement C5a; D010047:Ovalbumin