Complement C1q enhances homing-related responses of hematopoietic stem/progenitor cells

BACKGROUND: Previously, we reported that the complement cleavage fragments C3a and C5a are important modulators of trafficking of hematopoietic stem/progenitor cells (HSPCs). The aim of this study was to examine a possible role for complement component 1, subcomponent q (C1q) in HSPC migration. STUDY DESIGN AND METHODS: CD34+ HSPCs isolated from cord blood (CB), bone marrow (BM), and granulocyte–colony‐stimulating factor (G‐CSF)‐mobilized peripheral blood (mPB) were evaluated for the expression of C1q and its receptor for phagocytosis (C1qRp) using reverse transcription–polymerase chain reaction, Western blotting, and fluorescence‐activated cell sorting. Chemotactic responses and chemoinvasiveness toward stromal cell–derived factor (SDF)‐1 and expression of matrix metalloproteinase (MMP)‐9 were also examined after C1q stimulation. Moreover, G‐CSF– and zymosan‐induced mobilization was evaluated in C1q‐deficient mice. RESULTS: C1q was expressed in CD34+ cells from mPB, but not from CB or steady‐state BM; however, stimulation of the latter with G‐CSF induced C1q expression. C1qRp receptor was found on BM, CB, and mPB CD34+ cells and more mature ex vivo expanded myeloid and megakaryocytic precursors. Although C1q itself was not a chemoattractant for HSPCs, it primed/enhanced the chemotactic response of CD34+ cells to a low SDF‐1 gradient and their chemoinvasion across the reconstituted basement membrane Matrigel and increased secretion of MMP‐9 by these cells. Moreover, in in vivo studies C1q‐deficient mice were found to be easy G‐CSF mobilizers compared to wild‐type mice and normal zymosan mobilizers. CONCLUSION: We demonstrated that C1q primes the responses of CD34+ HSPCs to an SDF‐1 gradient, which may enhance their ability to stay within BM niches, suggesting that the C1q/C1qRp axis contributes to HSPC homing/retention in BM.