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.
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.


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.


CONCLUSIONS
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.
Epperly
Michael W
MW
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, PA 15213, USA.
Shields
Donna
D
Niu
Yunyun
Y
Carlos
Timothy
T
Greenberger
Joel S
JS
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D018821:CD18 Antigens / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D005720:Gamma Rays; D017353:Gene Deletion; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006720:Homozygote; D008136:Longevity; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D016177:Macrophage-1 Antigen / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011828:Radiation Chimera; D011995:Recombination, Genetic; D013997:Time Factors; D014916:Whole-Body Irradiation
D018821:CD18 Antigens; D016177:Macrophage-1 Antigen