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Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4 axis: further evidence that innate immunity orchestrates the mobilization of hematopoietic stem/progenitor cells.
Exp Hematol. 2010 Apr; 38(4):321-32.EH

Abstract

OBJECTIVE

Having previously demonstrated that the complement system modulates mobilization of hematopoietic stem/progenitor cells (HSPC) in mice, we investigated the involvement of C5 cleavage fragments (C5a/(desArg)C5a) in human HSPC mobilization.

MATERIALS AND METHODS

C5 cleavage fragments in the plasma were evaluated by enzyme-linked immunosorbent assay using human anti-(desArg)C5a antibody, and expression of the C5a/(desArg)C5a receptor (CD88) in hematopoietic cells by flow cytometry. We also examined the chemotactic responses of hematopoietic cells to C5 cleavage fragments and expression of stromal cell-derived factor-1 (SDF-1)-degrading proteases that perturb retention of HSPC in bone marrow, namely matrix metalloproteinase (MMP)-9, membrane type (MT) 1-MMP, and carboxypeptidase M.

RESULTS

We found that plasma levels of (desArg)C5a are significantly higher in patients who are good mobilizers and correlate with CD34(+) cell and white blood cell counts in mobilized peripheral blood. C5 cleavage fragments did not chemoattract myeloid progenitors (colony-forming unit granulocyte-macrophage), but (desArg)C5a did strongly chemoattract mature nucleated cells. Consistently, CD88 was not detected on CD34(+) cells, but appeared on more mature myeloid precursors, monocytes, and granulocytes. Moreover, granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells and polymorphonuclear cells had a significantly higher percentage of cells expressing CD88 than nonmobilized peripheral blood. Furthermore, C5a stimulation of granulocytes and monocytes decreased CXCR4 expression and chemotaxis toward an SDF-1 gradient and increased secretion of MMP-9 and expression of MT1-MMP and carboxypeptidase M.

CONCLUSION

C5 cleavage fragments not only induce a highly proteolytic microenvironment in human bone marrow, which perturbs retention through the CXCR4/SDF-1 axis, but also strongly chemoattracts granulocytes, promoting their egress into mobilized peripheral blood, which is crucial for subsequent mobilization of HSPC.

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Authors+Show Affiliations

Jalili A
Canadian Blood Services R & D, University of Alberta, Edmonton, Alberta, Canada.
Shirvaikar N
No affiliation info available
Marquez-Curtis L
No affiliation info available
Qiu Y
No affiliation info available
Korol C
No affiliation info available
Lee H
No affiliation info available
Turner AR
No affiliation info available
Ratajczak MZ
No affiliation info available
Janowska-Wieczorek A
No affiliation info available

MeSH

AnimalsCatechinCells, CulturedChemokine CXCL12ChemotaxisComplement C5Complement C5aEnzyme-Linked Immunosorbent AssayFlow CytometryGene Expression RegulationGranulocyte Colony-Stimulating FactorHematopoietic Stem Cell MobilizationHematopoietic Stem CellsHumansImmunity, InnateLymphoma, Non-HodgkinMicePeptide FragmentsReceptor, Anaphylatoxin C5aReceptors, CXCR4Up-Regulation

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20153802

Citation

Jalili, Ali, et al. "Fifth Complement Cascade Protein (C5) Cleavage Fragments Disrupt the SDF-1/CXCR4 Axis: Further Evidence That Innate Immunity Orchestrates the Mobilization of Hematopoietic Stem/progenitor Cells." Experimental Hematology, vol. 38, no. 4, 2010, pp. 321-32.
Jalili A, Shirvaikar N, Marquez-Curtis L, et al. Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4 axis: further evidence that innate immunity orchestrates the mobilization of hematopoietic stem/progenitor cells. Exp Hematol. 2010;38(4):321-32.
Jalili, A., Shirvaikar, N., Marquez-Curtis, L., Qiu, Y., Korol, C., Lee, H., Turner, A. R., Ratajczak, M. Z., & Janowska-Wieczorek, A. (2010). Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4 axis: further evidence that innate immunity orchestrates the mobilization of hematopoietic stem/progenitor cells. Experimental Hematology, 38(4), 321-32. https://doi.org/10.1016/j.exphem.2010.02.002
Jalili A, et al. Fifth Complement Cascade Protein (C5) Cleavage Fragments Disrupt the SDF-1/CXCR4 Axis: Further Evidence That Innate Immunity Orchestrates the Mobilization of Hematopoietic Stem/progenitor Cells. Exp Hematol. 2010;38(4):321-32. PubMed PMID: 20153802.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4 axis: further evidence that innate immunity orchestrates the mobilization of hematopoietic stem/progenitor cells. AU - Jalili,Ali, AU - Shirvaikar,Neeta, AU - Marquez-Curtis,Leah, AU - Qiu,Yuanyuan, AU - Korol,Chris, AU - Lee,HakMo, AU - Turner,A Robert, AU - Ratajczak,Mariusz Z, AU - Janowska-Wieczorek,Anna, Y1 - 2010/02/12/ PY - 2009/09/18/received PY - 2010/01/15/revised PY - 2010/02/05/accepted PY - 2010/2/16/entrez PY - 2010/2/16/pubmed PY - 2010/4/16/medline SP - 321 EP - 32 JF - Experimental hematology JO - Exp Hematol VL - 38 IS - 4 N2 - OBJECTIVE: Having previously demonstrated that the complement system modulates mobilization of hematopoietic stem/progenitor cells (HSPC) in mice, we investigated the involvement of C5 cleavage fragments (C5a/(desArg)C5a) in human HSPC mobilization. MATERIALS AND METHODS: C5 cleavage fragments in the plasma were evaluated by enzyme-linked immunosorbent assay using human anti-(desArg)C5a antibody, and expression of the C5a/(desArg)C5a receptor (CD88) in hematopoietic cells by flow cytometry. We also examined the chemotactic responses of hematopoietic cells to C5 cleavage fragments and expression of stromal cell-derived factor-1 (SDF-1)-degrading proteases that perturb retention of HSPC in bone marrow, namely matrix metalloproteinase (MMP)-9, membrane type (MT) 1-MMP, and carboxypeptidase M. RESULTS: We found that plasma levels of (desArg)C5a are significantly higher in patients who are good mobilizers and correlate with CD34(+) cell and white blood cell counts in mobilized peripheral blood. C5 cleavage fragments did not chemoattract myeloid progenitors (colony-forming unit granulocyte-macrophage), but (desArg)C5a did strongly chemoattract mature nucleated cells. Consistently, CD88 was not detected on CD34(+) cells, but appeared on more mature myeloid precursors, monocytes, and granulocytes. Moreover, granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells and polymorphonuclear cells had a significantly higher percentage of cells expressing CD88 than nonmobilized peripheral blood. Furthermore, C5a stimulation of granulocytes and monocytes decreased CXCR4 expression and chemotaxis toward an SDF-1 gradient and increased secretion of MMP-9 and expression of MT1-MMP and carboxypeptidase M. CONCLUSION: C5 cleavage fragments not only induce a highly proteolytic microenvironment in human bone marrow, which perturbs retention through the CXCR4/SDF-1 axis, but also strongly chemoattracts granulocytes, promoting their egress into mobilized peripheral blood, which is crucial for subsequent mobilization of HSPC. SN - 1873-2399 UR - https://www.unboundmedicine.com/medline/citation/20153802/Fifth_complement_cascade_protein__C5__cleavage_fragments_disrupt_the_SDF_1/CXCR4_axis:_further_evidence_that_innate_immunity_orchestrates_the_mobilization_of_hematopoietic_stem/progenitor_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-472X(10)00046-9 DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓38 ↑42]

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