Stimulation of human rheumatoid synovial cells by non-lethal complement membrane attack

Abstract

The effects of non-lethal complement attack on cultured human rheumatoid synovial cells have been investigated by measuring a variety of parameters. Within 3-4 min of initiating non-lethal complement membrane attack there was a rise in reactive oxygen metabolite release from cultured synovial cells, which slowly returned to basal levels over a period of 45 min. The response was dependent on the formation of the complete C5b-9 complex. Prostaglandin E2 was also released during non-lethal attack in a biphasic manner, an early phase of release occurring within the first hour and a second, larger phase commencing at 4 hr and rising to levels of over 1000 ng/10(6) cells at 24 hr, compared to control levels at this time of less than 100 ng/10(6) cells. This response was dependent on the formation of the C5b-8 complex but did not require C9. Removal of extracellular calcium reduced release of prostaglandin E2 to background levels, and inclusion of an inhibitor of protein synthesis abolished the second phase of release but not the first phase. Non-lethal attack caused release of small amounts of leukotriene B4 but no detectable release of tumour necrosis factor.