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

Abstract

Summary C5a, a 74 amino acid peptide cleaved from the complement protein C5, is an extremely potent anaphylatoxin. Expression of the receptor for the anaphylatoxin C5a (C5aR) has been thought to be restricted to cells of myeloid origin. However, recent evidence suggests that the C5aR is also expressed in hepatocytes as well as in pulmonary epithelial, endothelial and smooth muscle cells. In the present study, we investigated the tissue distribution of C5aR by immunohistochemistry in normal human lung, liver, intestine and kidney using well‐defined monoclonal antibodies (mAbs) directed against the extracellular N‐terminus of the receptor. In all tissues examined, macrophages displayed an abundant expression of C5aR protein. However, in the normal human lung, C5aR expression was not detectable in bronchial and alveolar epithelial cells or in vascular smooth muscle or endothelial cells. In the normal human liver, no C5aR protein was detected in hepatocytes, whereas Kupffer cells strongly expressed the C5aR. In normal human kidney, the C5aR was detectable only in proximal tubular cells. C5aR gene transcription in Kupffer cells and proximal tubular cells was confirmed by in situ hybridization. Thus, our results point to an as yet unknown role of the C5aR in normal renal physiology. In the normal lung and liver, however, previous evidence for the ubiquitous expression of C5aR in epithelial, endothelial and smooth muscle cells in situ should be re‐evaluated.

Decay-accelerating factor but not CD59 limits experimental immune-complex glomerulonephritis

“…Both are located on proximal tubular epithelial cells, [21][22][23] while in the glomerulus, C3a and C5a receptors appear specific to podocytes and mesangial cells, respectively. 16,21,24,25 Systemic administration of lipopolysaccharide can markedly increase mesangial C5aR expression, which is dependent on urokinase receptor activation.…”

Expression of the Complement Anaphylatoxin C3a and C5a Receptors on Bronchial Epithelial and Smooth Muscle Cells in Models of Sepsis and Asthma

“…The sections shown are ϫ63 magnification. (63,64). These differences may be explained by the types of reagents used for the immunohistochemistry and in situ hybridization experiments and the level of sensitivity required to detect basal C5aR expression in normal human lung.…”

C5a promotes development of experimental lupus nephritis which can be blocked with a specific receptor antagonist

“…C5aR activation on these cells can contribute to the inflammation in many diseases, such as the reverse Arthus reaction [14] and sepsis [15]. Of relevance to the kidney is the finding of C5aR in cultured renal mesangial and proximal tubular epithelial cells [16][17][18], and that C5a signaling through C5aR has been shown to be important in the tubulointerstitial injury in a model of immune complex-mediated glomerulonephritis (GN) [19]. As for humans, the expression of C5aR has been observed to be increased in the kidneys of patients with lupus nephritis [20], supporting its potential relevance in disease pathogenesis.…”