Initiation of Bone Resorption by the Classical and Alternative C Pathways and Its Mediation by Prostaglandins

Abstract

Activation of C by immunoglobulins reactive with cell surface antigens stimulated synthesis of prostaglandin E and resultant release of 45Ca from organ cultures of fetal rat bones labeled in utero. Absorption of the C source (rabbit serum) with rat spleen cells or dilution of C abolished this activity which was, however, restored by addition of immunoglobulin preparations from sera of rabbits immunized with either rat erythrocytes or sonicated fetal rat bones. The active reconstitution factors were present in the 50% (NH4)2SO4 cut of the antisera and were eluted from Sephadex G-200 in both the 19S and 7S fractions and from DEAE cellulose in the IgG-containing fraction. The C-dependent resorption of bone by the F(ab')2 fragments of the IgG antibody implicated a role for the alternative C pathway in this event. Complete inhibition of this biologic effect by indomethacin and detection of enhanced levels of prostaglandin E in the media of cultures containing antibody and C demonstrated a role for prostaglandins as mediators in the destruction of bone initiated by immune activation of C.