Expression of c5a receptors on bone marrow stromal cells and biological responses to c5a

C5a anaphylatoxin is a 74- residue glycoprotein generated as a cleavage product of the fifth component of complement (C5) and is a potent activator of various inflammatory and immuno-modulatory responses. C5a receptors are expressed on many different cell populations such as monocytes, granulocytes, epithelial cells and endothelial cells. This study examined the expression of C5a receptors on bone marrow stromal cells and biological responses to C5a. C5a receptors were detected on a mouse bone marrow stromal cell line and human bone marrow stromal cells by flow cytometry and western blots. Previously, C5a was shown to regulate cytokine production from human bronchial epithelial cells. C5a induced secretion of IL-6 was examined from human bone marrow stromal cells. Interestingly, the addition of C5a(l .g/ml) to human stromal cells did not increase the secretion of IL-6 over non-treated cells. However, pre-treatment of the stromal cells with IL-1 (0.1 ng/ml) significantly increased the release of IL-6 when the cells were exposed to C5a compared to non-treated, C5a treated or IL-1 treated stromal cells. The C5a mediated increase in IL-6 release from IL-1 pre-treated stromal cells was reduced in the presence of neutralizing C5a receptor antibody. These results show that bone marrow stromal cells constitutively express C5a receptors, but a biological response (IL-6 release) to C5a occurs only after an inflammatory priming signal (IL-1). The results suggest that C5a may play a role in altering hematopoiesis via factor production by microenvironmental stromal cells.