The Arthus reaction in rodents: species-specific requirement of complement.
We induced reverse passive Arthus (RPA) reactions in the skin of rodents and found that the contribution of complement to immune complex-mediated inflammation is species specific. Complement was found to be necessary in rats and guinea pigs but not in C57BL/6J mice. In rats, within 4 h after initiation of an RPA reaction, serum alternative pathway hemolytic titers decreased significantly below basal levels, whereas classical pathway titers were unchanged. Thus the dermal reaction proceeds coincident with systemic activation of complement. The serine protease inhibitor BCX 1470, which blocks the esterolytic and hemolytic activities of the complement enzymes Cls and factor D in vitro, also blocked development of RPA-induced edema in the rat. These data support the proposal that complement-mediated processes are of major importance in the Arthus reaction in rats and guinea pigs, and suggest that BCX 1470 will be useful as an anti-inflammatory agent in diseases where complement activation is known to be detrimental.
Szalai
A J
AJ
Department of Medicine, University of Alabama, Birmingham 35294, USA. Alex.Szalai@ccu.uab.edu
Digerness
S B
SB
Agrawal
A
A
Kearney
J F
JF
Bucy
R P
RP
Niwas
S
S
Kilpatrick
J M
JM
Babu
Y S
YS
Volanakis
J E
JE
D000818:Animals; D001183:Arthus Reaction / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D003167:Complement Activation / Q000187:drug effects; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology; D011416:Complement Factor D / Q000037:antagonists & inhibitors; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013045:Species Specificity; D013876:Thiophenes / Q000494:pharmacology*
C402682:BCX 1470; D003174:Complement C1 Inactivator Proteins; D015842:Serine Proteinase Inhibitors; D013876:Thiophenes; D003165:Complement System Proteins; C493488:CFD protein, human; D011416:Complement Factor D; C493491:complement factor D, mouse