This work was supported by a postdoctoral research fellowship to AJ, an operating grant from the Canadian Blood Services/Canadian Institutes for Health Research to AJW, and a National Institutes of Health grant (R01 DK074720) to MZR.
TRANSPLANTATION AND CELLULAR ENGINEERING
Complement C1q enhances homing-related responses of hematopoietic stem/progenitor cells
Article first published online: 30 APR 2010
© 2010 American Association of Blood Banks
Volume 50, Issue 9, pages 2002–2010, September 2010
How to Cite
Jalili, A., Marquez-Curtis, L., Shirvaikar, N., Wysoczynski, M., Ratajczak, M. and Janowska-Wieczorek, A. (2010), Complement C1q enhances homing-related responses of hematopoietic stem/progenitor cells. Transfusion, 50: 2002–2010. doi: 10.1111/j.1537-2995.2010.02664.x
- Issue published online: 1 SEP 2010
- Article first published online: 30 APR 2010
- Received for publication December 2, 2009; revision received February 22, 2010; and accepted February 24, 2010.
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.