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Inflammatory mechanisms in the passive cutaneous anaphylactic reaction in the rabbit: evidence that novel mediators are involved
Author(s) -
Hellewell Paul G.,
Jose Peter J.,
Williams Timothy J.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb13424.x
Subject(s) - chemistry , bradykinin , edema , vasodilation , vascular permeability , prostaglandin , sensitization , exudate , pharmacology , fibrin , ovalbumin , erythema , arthus reaction , eicosanoid , endocrinology , medicine , immunology , inflammation , antigen , pathology , biochemistry , arachidonic acid , receptor , enzyme
1 We have examined the mechanisms of local oedema formation in the passive cutaneous anaphylactic (PCA) reaction in the rabbit. 2 IgE‐containing antiserum was injected i.d. and allowed to sensitize skin sites for periods up to 240 h. Antigen (bovine gamma globulin) was injected i.d. or i.v. and local oedema formation assessed by the accumulation of i.v. injected 125 I‐labelled rabbit serum albumin. Potential inhibitors were mixed with antigen prior to i.d. injection or were administered i.v. 3 Maximum oedema formation was observed when a sensitization period of 48–72 h was used. Oedema formation in the PCA reaction was of short duration with a t 1/2 of approximately 15 min. No evidence of late oedema formation (up to 6 h) was found. 4 Local oedema formation in the PCA was reduced by indomethacin suggesting that vasodilator, oedema‐potentiating prostaglandins were released. However, it was likely that other vasodilators were also generated. 5 Antihistamines were poor inhibitors of oedema formation as were PAF antagonists, a 5‐lipoxygenase inhibitor, a kallikrein inhibitor, a bradykinin antagonist and anti‐C5a antibody. 6 Local oedema formation in the PCA was partially reduced by neutrophil depletion and colchicine suggesting that neutrophil‐dependent mediators were involved. 7 Exudate fluid from anaphylactic reactions in the rabbit peritoneal cavity contained permeability‐increasing activity when injected into rabbit skin. This activity is now being characterized. 8 A vasodilator prostaglandin appears to be released in the rabbit PCA reaction but none of the established permeability‐increasing mediators appears to be involved. Thus, there may be novel inflammatory mediators generated in this reaction which may have relevance for human allergic skin diseases.