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 - PubMed (original) (raw)

Comparative Study

. 2006 Jul-Aug;20(4):431-8.

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Comparative Study

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

Michael W Epperly et al. In Vivo. 2006 Jul-Aug.

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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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