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.


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.


CONCLUSIONS
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.
Jalili
Ali
A
Canadian Blood Services, Research & Development, and the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Marquez-Curtis
Leah
L
Shirvaikar
Neeta
N
Wysoczynski
Marcin
M
Ratajczak
Mariusz
M
Janowska-Wieczorek
Anna
A
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D015922:Complement C1q / Q000378:metabolism* / Q000494:pharmacology*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor; D015922:Complement C1q
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