Research Abstract

Blood. 2006;107:835-840
© 2006 by The American Society of Hematology

ß-Glucan enhances complement-mediated hematopoietic recovery
after bone marrow injury

Daniel E. Cramer, Daniel J. Allendorf, Jarek T. Baran, Richard Hansen, Jose Marroquin, Bing Li, Janina Ratajczak, Mariusz Z. Ratajczak, and Jun Yan

Abstract
Myelotoxic injury in the bone marrow (BM) as a consequence of total body
irradiation (TBI) or granulocyte colonystimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM stroma (stroma-iC3b). In the present study, we have examined how stromaiC3b 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 ß-glucan, a ligand for the CR3 lectin–like domain (LLD), in the priming of CR3+ HPC is suggested. Soluble yeast ß-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 ß-glucan in the restoration of hematopoiesis following injury.