A DEFECT IN THE INFLAMMATION-PRIMED MACROPHAGE-ACTIVATION CASCADE IN OSTEOPETROTIC RATS

Macrophages were activated by administration of lysophosphatidylcholin e (lyse-Pc) or dodecylglycerol (DDG) to wild-type rats but not in oste opetrotic (op) mutant rats. In vitro treatment of wild-type rat perito neal cells with lyse-Pc or DDC efficiently activated macrophages where as treatment of op mutant rat peritoneal cells with lyse-Pc or DDG did not activate macrophages. The inflammation-primed macrophage activati on cascade in rats requires participation of B lymphocytes and vitamin D binding protein (DBP). Lyse-Pc-inducible beta-galactosidase of wild -type rat B lymphocytes can convert DBP to the macrophage-activating f actor (MAF), whereas B lymphocytes of the op mutant rats were shown to be deficient in lyse-Pc-inducible beta-galactosidase. DBP is conserve d among mammalian species. Treatment of human DBP (Gc1 protein) with c ommercial glycosidases yields an extremely high titrated MAP-as assaye d on mouse and rat macrophages. Because the enzymatically generated MA F (GcMAF) bypasses the role of lymphocytes in macrophage activation, t he op mutant rat macrophages were efficiently activated by administrat ion of a small quantity (100 pg/rat) of GcMAF. Likewise, in vitro trea tment of op rat peritoneal cells with as little as 40 pg GcMAF/ml acti vated macrophages.