Anti-CD11b antibody prevents immunopathologic changes in viable moth-eaten bone marrow chimeric mice.
The effect of in vivo treatment with anti-CD11b (MAC-1) antibody (Ab) was examined in an inflammatory disease model, the viable moth-eaten (mev) mutant mouse. The autosomal recessive mev gene occurred spontaneously as a point mutation of the hematopoietic cell protein tyrosine phosphatase in C57BL/6 mice. Homozygotes (mev/mev) develop a chronic myelomonocytic inflammation, involving accumulation of myelomonocytic cells in lungs and skin, resulting in interstitial pneumonitis and severe edema in the paws. These mice also exhibit abnormalities in lymphoid development, thymic atrophy, with T cell and NK cell dysfunction. These inflammatory changes are transferrable by bone marrow cells of mev/mev mice, indicating that mev mutation is due to a stem cell defect in the myelomonocytic pathway. An anti-CD-11b (5C6) Ab inhibited the immunopathologic changes in the bone marrow chimeras, when the Ab treatment was initiated on day -1 or day 0 of the bone marrow transplant. The lungs, paws, and thymus all remained normal after treatment. Furthermore, the Ab also delayed the onset of the mev syndromes when the Ab was given 10 days after the bone marrow transfer. Therefore anti-CD11b Ab inhibited inflammation both prophylactically and therapeutically, and restored normal function of T and NK cells in this disease model. These results support the contention that CD11b molecules expressed in the myelomonocytic cells play a critical role in this naturally occurring inflammatory disease.
Koo
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GC
Department of Immunology Research, Merck Research Laboratories, Merck and Co., Rahway, NJ 07065.
Rosen
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H
Sirotina
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A
Ma
X D
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Shultz
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LD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D002678:Chimera; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology; D016177:Macrophage-1 Antigen; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D017027:Protein Tyrosine Phosphatases