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CD18 regulates neutrophil production in the bone marrow
Author(s) -
Gomez John C.,
Doerschuk Claire M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a178-c
Subject(s) - cd18 , haematopoiesis , bone marrow , neutrophilia , biology , granulocyte , cd34 , myeloid , immunology , progenitor cell , microbiology and biotechnology , stem cell , integrin alpha m , flow cytometry
Deficiency of the leukocyte integrin CD18 leads to functional defects in neutrophils, neutrophilia and myeloid hyperplasia in the bone marrow (BM). To study the role of CD18 in neutrophil production, lethally irradiated wild type (WT) recipients were reconstituted with a 1:4 or 4:1 mixture of WT and CD18−/− fetal liver cells. In both groups of chimeric animals, the proportion of CD18−/− neutrophils in the circulation and BM was higher than the proportion of CD18−/− donor cells in the transplant, and the percentage of CD18−/− leukocytes that were neutrophils was greater compared with WT leukocytes. The proportion of apoptotic (annexin V‐positive) BM cells expressing the granulocyte marker Gr‐1 was less in CD18−/− than in WT BM cells. Surprisingly, the proportion of B cells that were CD18−/− in the chimeric mice was greater than the proportion of CD18−/− donor cells. Conversely, the proportion of CD18−/− T cells was lower than predicted. When WT and CD18−/− hematopoietic stem cells were grown in vitro, the number of Gr‐1+ cells was greater in CD18−/− than WT cultures, due to a greater number of annexin V‐negative Gr‐1+ cells. The data suggest that CD18 regulates neutrophil production in the BM by regulating the survival of neutrophil precursors and/or commitment of hematopoietic progenitors to leukocyte lineages. Supported by PHS R37HL048160 and T32HL007415.