Joint fluid leukocyte activation by preformed immune complexes

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Abstract
Acute synovitis was induced in rabbit knee joints by intraarticular injection of preformed bovine serum albumin (BSA)-anti BSA immune complexes (ICs). Polymorphonuclear granulocytes (PMNGs) which had migrated into joints injected with ICs were degranulated and contained ICs as revealed by electron microscopy and were activated as revealed by the measurement of chemiluminescence (CL). In contrast, leukocytes from control joints injected with BSA and normal rabbit serum as well as glycogen-elicited peritoneal leukocytes did not display any morphological changes and did not show CL. Compared to cells from other sources, leukocytes from IC joints showed a decreased CL response when stimulated in vitro with ICs but not with opsonized zymosan, suggesting a stimulus-specific modification of the PMNG responsiveness. Inhibition experiments showed that oxygen radicals and formation of arachidonate metabolites, mainly of the lipoxygenase pathway, were involved in the CL response of the IC-stimulated joint fluid PMNGs. Our observations on morphology, activity, and responsiveness of emigrated cells from the various sources suggest, together with previous observations, that the reaction of leukocytes in IC-induced synovitis consists of an initial migration phase not related to an increased CL and a subsequent activation phase characterized by degranulation, phagocytosis of ICs and increased CL.