Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma

The presence of the complement-derived anaphylatoxin peptides, C3a and C5a, in the lung can induce respiratory distress characterized by contraction o f the smooth muscle walls in bronchioles and pulmonary arteries and aggrega tion of platelets and leukocytes in pulmonary vessels. C3a and C5a mediate these effects by binding to their specific receptors, C3aR and C5aR, respec tively. The cells that express these receptors in the lung have not been th oroughly investigated, nor has their expression been examined during inflam mation. Accordingly, C3aR and C5aR expression in normal human and murine lu ng was determined in this study by immunohistochemistry and in situ hybridi zation. In addition, the expression of these receptors was delineated in mi ce subjected to LPS- and OVA-induced models of inflammation. Under noninfla med conditions, C3aR and C5aR protein and mRNA were expressed by bronchial epithelial and smooth muscle cells of both human and mouse lung. C3aR expre ssion increased significantly on both bronchial epithelial and smooth muscl e cells in mice treated with LPS; however, in the OVA-challenged animals on ly the bronchial smooth muscle cells showed increased C3aR expression. C5aR expression also increased significantly on bronchial epithelial cells in m ice treated with LPS, but was not elevated in either cell type in the OVA-c hallenged mice. These results demonstrate the expression of C3aR and C5aR b y cells endogenous to the lung, and, given the participation of bronchial e pithelial and smooth muscle cells in the pathology of diseases such as seps is and asthma, the data suggest a role for these receptors during lung infl ammation.