Functional C5a receptors on murine bone marrow-derived stromal cells enhance localization of a murine lympho-hematopoietic cell line

C5a anaphylatoxin, a 74-residue glycopoly pep tide generated as a cleavage product of the fifth component of complement (C5), is known to be a potent activator and chemotactic agent of monocytes and neutrophils. To determine if C5a can affect the interactions of lympho-hematopoietic cells with the bone marrow stromal microenvironment, a cloned murine stromal-dependent pro-B cell line, TAJ.B11, and a cloned murine stromal cell line, W/W2.G5, were used. Under normal growth conditions a portion of TAJ.B11 cells migrate under the stromal cell line. The addition of C5a or C5a decapeptide agonist had no effect on the number of migrating TAJ.B11 cells(89% ± 8 SEM migrating cells of untreated control). Pretreatment of the stromal cell line with recombinant human IL-1β resulted in a decrease in the number of migrating TAJ.B11 cells (63% ± 6). However, the addition of C5a or agonist peptide to the IL-1β pretreated stromal cells resulted in a significant increase in the number of migrating TAJ.B11 cells (223% ± 21 of IL-1 treated control). C5a receptors on murine and human stromal cells were demonstrated by flow cytometry and western blots. IL-1bβ pretreatment of the stromal cells did not lead to a significant change in the expression of C5aR, The results show that C5aR is constitutively expressed on bone marrow derived stromal cells and that C5a can enhance migration of a hematopoietic progenitor cell line following activation of the receptor on the stromal cells.