THE ROLES OF COMPLEMENT RECEPTORS TYPE-1 (CR-1, CD35) AND TYPE-3 (CR3, CD11B CD18) IN THE REGULATION OF THE IMMUNE COMPLEX-ELICITED RESPIRATORY BURST OF POLYMORPHONUCLEAR LEUKOCYTES IN WHOLE-BLOOD/

The binding of immune complexes (IC) to polymorphonuclear leukocytes ( PMN) and the consequent respiratory burst (RE) were investigated in wh ole blood cell preparations suspended in 75% human serum, using flow c ytometry Blockade of the complement receptor (CR)1 receptor sites for C3b on whole blood cells using the monoclonal antibody (mAb) 3D9 resul ted in a 1.9-fold increase in the IC-elicited PMN RE after 5 min of in cubation, rising to 3.1-fold after 40 min. This enhancement was not du e to increased IC deposition on PMN. Blockade of CR3 abrogated the mAb 3D9-induced rise in RE activity and inhibited the IC binding to PMN i n a whole blood cell preparation, with or without mAb 3D9, by approxim ately 40% from 15-40 min while reducing their RE over 40 min to approx imately one third. Blockade of CR1 on either erythrocytes (E) or leuko cytes, before mixing the populations, revealed that the potentiation o f the RE by mAb 3D9 was associated with abrogation of E-CR1 function, whereas blockade of leukocyte-CR1 had a diminishing effect. Exposure t o IC at high concentrations induced release of both specific and azuro philic granule contents from PMN. The latter was CR3 dependent in that blockade of the receptor inhibited the lactoferrin release by one thi rd during 40 min of incubation. In conclusion, CR3 plays a significant role in the IC-mediated generation of an RE and release of specific g ranules by PMN, while CR1 on whole blood cells, primarily E CR1, restr icts the IC-elicited RE in PMN. We propose that CR1 in whole blood pro motes the degradation of IC-bound iC3b to C3dg, thereby rendering the IC inaccessible for binding to CR3.