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.

C5a receptor signalling in dendritic cells controls the development of maladaptive Th2 and Th17 immunity in experimental allergic asthma

“…This is in sharp contrast to our previous findings and suggests that in vivo C5aR-activation on other cell types besides DCs such as tissue resident alveolar macrophages or airway epithelial cells has to be considered, both of which express C5aR 34,35 and exert immunoregulatory properties. Indeed, airway epithelial cells secrete several cytokines, including GM-CSF, TSLP, IL-25, IL-33, and IL-1 family members, upon allergen contact that promote DC maturation enabling them to differentiate naive T cells into Th2 effector cells.…”

Membrane Attack Complex Contributes to Destruction of Vascular Integrity in Acute Lung Allograft Rejection

“…This injury has been attributed to biological effects of C5a and MAC. C5aR has been localized by immunohistology on bronchial and alveolar epithelial cells as well as vascular smooth muscle and endothelial cells of human lung tissue (26,28,57,58). The potential for tissue activation through the C5aR has been verified for endothelial cells in culture.…”

Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions

“…C3aR-positive bone marrow-derived cells that participate in host immune responses include mast cells, eosinophils, basophils, neutrophils, dendritic cells (DCs), macrophages, T cells, and B cells (3)(4)(5)(6). The C3aR is also expressed in nonmyeloid tissues, including kidney, brain, lung, heart, and liver (7)(8)(9)(10).…”