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 ( me(v)) mutant mouse. The autosomal recessive me(v) gene occurred spont aneously as a point mutation of the hematopoietic cell protein tyrosin e phosphatase in C57BL/6 mice. Homozygotes (me(v)/me(v)) develop a chr onic myelomonocytic inflammation, involving accumulation of myelomonoc ytic cells in lungs and skin, resulting in interstitial pneumonitis an d severe edema in the paws. These mice also exhibit abnormalities in l ymphoid development, thymic atrophy, with T cell and NK cell dysfuncti on. These inflammatory changes are transferrable by bone marrow cells of me(v)/me(v) mice, indicating that me(v) mutation is due to a stem c ell defect in the myelomonocytic pathway. An anti-CD-11b (5C6) Ab inhi bited the immunopathologic changes in the bone marrow chimeras, when t he Ab treatment was initiated on day-1 or day 0 of the bone marrow tra nsplant. The lungs, paws, and thymus all remained normal after treatme nt. Furthermore, the Ab also delayed the onset of the me(v) syndromes when the Ab was given 10 days after the bone marrow transfer. Therefor e anti-CD11b Ab inhibited inflammation both prophylactically and thera peutically, and restored normal function of T and NK cells in this dis ease model. These results support the contention that CD11b molecules expressed in the myelomonocytic cells play a critical role in this nat urally occurring inflammatory disease.