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  • Title: Bone marrow from CD18-/- (MAC-1-/-) homozygous deletion recombinant negative mice demonstrates increased longevity in long-term bone marrow culture and decreased contribution to irradiation pulmonary damage.
    Author: Epperly MW, Shields D, Niu Y, Carlos T, Greenberger JS.
    Journal: In Vivo; 2006; 20(4):431-8. PubMed ID: 16900771.
    Abstract:
    BACKGROUND: Bone marrow macrophage surface expression of CD18 (MAC-1, LFA1) is involved in cellular binding to V-CAM-1 and V-CAM-2 adhesion molecules expressed on endothelial cells. We sought to determine if this interaction affected the growth of marrow in long-term bone marrow cultures (LTBMCs) and macrophage migration to the irradiated lung in pulmonary fibrosis/organizing alveolitis. MATERIALS AND METHODS: Continuous bone marrow cultures from CD18-/- and CD18+/+ littermates were established. Bone marrow migration to the irradiated lung was quantitated in CD18+/+ or CD18-/- marrow chimeric mice. Anti-macrophage antibodies were administered to block monocyte/macrophage migration after lung irradiation. RESULTS: CD18-/- LTBMCs demonstrated significantly increased longevity (over 20 weeks) of production of multilineage hematopoietic progenitor cells, total non-adherent cells and macrophage progenitors compared to those derived from CD18+/+ littermates (10 weeks). C57BL/6J female mice chimeric for male CD18-/- bone marrow showed improved (50%) survival at 120 days after pulmonary radiation compared to female mice chimeric for male CD18+/+ bone marrow (0.0%). Intraperitoneal injections (daily for 15 days) of an anti-macrophage antibody on days 80-98 after 20 Gy total lung irradiation resulted in reduction of macrophage migration to the lungs and increased survival. CONCLUSION: The data demonstrate a complex role of CD18 (MAC-1) in macrophage progenitor and macrophage cellular interaction involving stromal cells of the bone marrow and lung.
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