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

Authors

  • Ali Jalili,

    1. From the Canadian Blood Services, Research & Development, and the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
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  • Leah Marquez-Curtis,

    1. From the Canadian Blood Services, Research & Development, and the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
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  • Neeta Shirvaikar,

    1. From the Canadian Blood Services, Research & Development, and the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
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  • Marcin Wysoczynski,

    1. From the Canadian Blood Services, Research & Development, and the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
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  • Mariusz Ratajczak,

    1. From the Canadian Blood Services, Research & Development, and the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
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  • Anna Janowska-Wieczorek

    1. From the Canadian Blood Services, Research & Development, and the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
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  • 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.

Anna Janowska-Wieczorek, MD, PhD, Department of Medicine, University of Alberta, CBS Edmonton Centre, 8249-114 Street NW, Edmonton, Alberta, Canada T6G 2R8; e-mail: anna.janowska@blood.ca.

Abstract

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.

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