Modulation of leukocyte recruitment and IL-8 expression by the membrane attack complex of complement (C5b-9) in a rabbit model of antigen-induced arthritis.
The complement system is thought to be a major physiological mediator of injury in a number of diseases including rheumatoid arthritis (RA). The membrane attack complex (MAC) of complement has been detected in RA tissue, suggesting that the MAC may be relevant to the pathogenesis of the disease. Deposition of sublytic concentrations of the MAC has been shown to promote the expression of proinflammatory mediators. In the present study, we utilized rabbits deficient in the complement protein C6 to elucidate the role of the MAC in mediating the pathogenesis of antigen-induced arthritis. Swelling, leukocyte accumulation, IL-8 expression, proteoglycan, and hydroxyproline content were assessed. Analysis of synovial tissue demonstrated a significant decrease in leukocyte influx and a parallel decrease in tissue associated IL-8 in joints of C6-deficient animals as compared to C6-sufficient animals. However, this did not correlate with the preservation of connective tissue. The results derived from this study provide evidence that the MAC has an important function in mediating leukocyte recruitment in antigen-induced arthritis but does not play a direct role in connective tissue breakdown.
Tramontini
Nicole L
NL
Inflammation Pharmacology, Pfizer Global Research, Ann Arbor, MI 48105, USA.
Kuipers
Paul J
PJ
Huber
Colleen M
CM
Murphy
Kerri
K
Naylor
Keith B
KB
Broady
Autumn J
AJ
Kilgore
Kenneth S
KS
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003183:Complement C6 / Q000172:deficiency* / Q000235:genetics; D015938:Complement Membrane Attack Complex / Q000172:deficiency* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D016209:Interleukin-8 / Q000096:biosynthesis*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism
D003183:Complement C6; D015938:Complement Membrane Attack Complex; D016209:Interleukin-8