Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury.
Myelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony-stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM stroma (stroma-iC3b). In the present study, we have examined how stroma-iC3b interacts with hematopoietic progenitor cells (HPCs) and the role of complement (C) and complement receptor 3 (CR3) in BM injury/repair. We demonstrate here that stroma-iC3b tethers HPCs via the inserted (I) domain of HPC complement receptor 3 (CR3, CD11b/CD18, Mac-1). Following irradiation, stroma-iC3b was observed in the presence of purified IgM and normal mouse serum (NMS), but not serum from Rag-2(-/-) mice, implicating a role for antibody (Ab) and the classic pathway of C activation. Furthermore, a novel role for soluble yeast beta-glucan, a ligand for the CR3 lectin-like domain (LLD), in the priming of CR3(+) HPC is suggested. Soluble yeast beta-glucan could enhance the proliferation of tethered HPCs, promote leukocyte recovery following sublethal irradiation, and increase the survival of lethally irradiated animals following allogeneic HPC transplantation in a CR3-dependent manner. Taken together, these observations suggest a novel role for C, CR3, and beta-glucan in the restoration of hematopoiesis following injury.
Cramer
Daniel E
DE
Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville, 580 South Preston St, Louisville, KY 40202, USA.
Allendorf
Daniel J
DJ
Baran
Jarek T
JT
Hansen
Richard
R
Marroquin
Jose
J
Li
Bing
B
Ratajczak
Janina
J
Ratajczak
Mariusz Z
MZ
Yan
Jun
J
D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000293:injuries* / Q000378:metabolism; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D003179:Complement C3b / Q000276:immunology* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology; D037102:Lectins; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012441:Saccharomyces cerevisiae; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D047071:beta-Glucans / Q000276:immunology / Q000378:metabolism*
D018821:CD18 Antigens; D004268:DNA-Binding Proteins; D007075:Immunoglobulin M; D037102:Lectins; D016177:Macrophage-1 Antigen; C499308:Rag2 protein, mouse; D047071:beta-Glucans; D003179:Complement C3b