Human rheumatoid synovial cell stimulation by the membrane attack complex and other pore-forming toxins in vitro: the role of calcium in cell activation.
The effects of non-lethal amounts of a variety of pore-forming agents on cultured human rheumatoid synovial cells (HRSC) have been investigated. Non-lethal complement membrane attack and non-lethal amounts of melittin, perforin and ionomycin all caused a biphasic release of prostaglandin E2 (PGE2) from HRSC, an early phase of release occurring within 1 hr and a second larger phase commencing after 4 hr and continuing over the 24-hr time-course. Removal of extracellular calcium abolished the release of PGE2 under all conditions of non-lethal attack. Modulation of G-protein activity reduced the second phase of release caused by non-lethal doses of the membrane-attack complex (MAC) from 800 ng/10(6) cells PGE2 to around 300 ng/10(6) cells. Non-lethal levels of the MAC also caused release of interleukin-6 (IL-6) from HRSC over the 24-hr time-course, with levels reaching 550 ng/10(6) cells at 24 hr compared to background levels of 200 ng/10(6) cells. No detectable release of IL-1 alpha could be measured at any time following non-lethal complement membrane attack. These results suggest a role for the MAC as an initiating mediator inducing the inflammation associated with rheumatoid arthritis.
Daniels
R H
RH
Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, U.K.
Williams
B D
BD
Morgan
B P
BP
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002118:Calcium / Q000276:immunology*; D002478:Cells, Cultured; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D015759:Ionomycin / Q000276:immunology; D008555:Melitten / Q000276:immunology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013583:Synovial Membrane / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000276:immunology
D015938:Complement Membrane Attack Complex; D007378:Interleukins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D010566:Virulence Factors, Bordetella; D054353:Perforin; D008555:Melitten; D015759:Ionomycin; D015232:Dinoprostone; D002118:Calcium