Systematic discovery and evaluation of complement inhibitors

Bauman, Norman; Brockman, John A.; Pease, Barbara S.; Elliott, W.J.; Colucci, D

doi:10.1016/0162-3109(81)90024-2

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…The rat RPA reaction has often been used as an in vivo model to test the efficacy of anti-inflammatory drugs (25)(26)(27)(28)(29)(30)(31)). Yet, despite FIGURE 6.…”

Section: Discussionmentioning

confidence: 99%

The Arthus Reaction in Rodents: Species-Specific Requirement of Complement

Szalai

Digerness²,

Agrawal

et al. 2000

The Journal of Immunology

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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.

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“…The rat RPA reaction has often been used as an in vivo model to test the efficacy of anti-inflammatory drugs (25)(26)(27)(28)(29)(30)(31)). Yet, despite FIGURE 6.…”

Section: Discussionmentioning

confidence: 99%

The Arthus Reaction in Rodents: Species-Specific Requirement of Complement

Szalai

Digerness²,

Agrawal

et al. 2000

The Journal of Immunology

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“…The Arthus reaction has been used as a screening tool for anti-inflammatory compounds in rats [1--4] and guinea pigs [5] because of these features of inflammation. In addition, the involvement of complement in the Arthus reaction has made the RPAR in guinea pigs a suitable assay for complement inhibitors [6].…”

Section: Introductionmentioning

confidence: 99%

“…Other characteristics of the reaction include erythema (hyperemia and/or hemorrhage), infiltration of neutrophils into vascular walls and surrounding tissue, damage of vascular integrity, hemorrhage and, at later stages, infiltration of mononuclear cells [7]. BAUMAN et al [6] used an average of two parameters of edema and one parameter of hemorrhage in order to assess the Arthus reaction. Because of the complexity of the Arthus reaction, the question arises whether the measurement of one parameter of the reaction can meaningfully characterize the potential inhibitory properties of a pharmacologic agent against RPAR.…”

Section: Introductionmentioning

confidence: 99%

Differential effects of pharmacologic agents on the reverse passive Arthus reaction in guinea pigs

et al. 1984

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Five different pharmacologic agents were examined for their effects upon edema, hemorrhage, and vascular infiltration by neutrophils in the reverse passive Arthus reaction (RPAR) in guinea pigs. Two agents, colchicine (3.0 mg/kg p.o.) and ibuprofen (100 mg/kg p.o.) significantly inhibited all three parameters of RPAR. Cobra venom factor (100 units/kg i.p.) inhibited edema and hemorrhage but it did not inhibit neutrophil infiltration. Aminophylline and sulfinpyrazone (100 mg/kg p.o.) inhibited only hemorrhage; they did not inhibit edema or neutrophil infiltration. The results from these studies with five chemically or biologically unrelated pharmacologic agents suggest that the RPAR in guinea pigs can be separated into its basic components (edema, hemorrhage, and neutrophilic infiltration) by selective inhibitors. Inhibition of edema and hemorrhage, or hemorrhage alone of the two-hour RPAR in guinea pigs is not dependent upon inhibition of neutrophilic infiltration.

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