The C5a receptor is expressed in normal renal proximal tubular but not in normal pulmonary or hepatic epithelial cells

C5a, a 74 amino acid peptide cleaved from the complement protein C5, is an extremely potent anaphylatoxin. Expression of the receptor for the anaphyla toxin C5a (CSaR) has been thought to be restricted to cells of myeloid orig in. However, recent evidence suggests that the C5aR is also expressed in he patocytes as well as in pulmonary epithelial, endothelial and smooth muscle cells. In the present study, we investigated the tissue distribution of C5 aR by immunohistochemistry in normal human lung, liver, intestine and kidne y using well-defined monoclonal antibodies (mAbs) directed against,the extr acellular N-terminus of the receptor. In all tissues examined, macrophages displayed an abundant expression of CSaR protein. However, in the normal hu man lung, CSaR expression was not detectable in bronchial and alveolar epit helial cells or in vascular smooth muscle or endothelial cells. In the norm al human liver, no CSaR protein was detected in hepatocytes, whereas Kupffe r cells strongly expressed the CSaR. In normal human kidney, the CSaR was d etectable only in proximal tubular cells. C5aR gene transcription in Kupffe r cells and proximal tubular cells was confirmed by in situ hybridization. Thus, our results paint to an as yet unknown role of the CSaR in normal ren al physiology. In the normal lung and liver, however, previous evidence for the ubiquitous expression of CSaR in epithelial, endothelial and smooth mu scle cells in situ Should be re-evaluated.