Effect of invertebrate serine proteinase inhibitors on carrageenan-induced pleural exudation and bradykinin release.

The carrageenan model of pleurisy is described as temporal plasma exudation (1-5 h) with extensive neutrophil infiltration and release of proteinases into the pleural cavity. The aim of this work was to study the effects of serine proteinase inhibitors on the inflammatory process induced by administration of carrageenan to the rat pleural cavity and on release of kinins in pleural exudate. Pleurisy was induced by injecting carrageenan and serine proteinase inhibitors simultaneously into the pleural cavity. The proteinase inhibitors used were: aprotinin, a plasma kallikrein inhibitor; recombinant leech derived tryptase inhibitor-2PL (LDTI-2PL), a plasmin inhibitor; Boophilus microplus trypsin inhibitors (BmTIs); trypsin; plasma kallikrein; plasmin and neutrophil elastase inhibitors; and a synthetic neutrophil elastase inhibitor (EIsynt). Administration of carrageenan with LDTI-2PL and BmTIs induced a marked increase in exudation (143% and 201%) and leukocyte migration (288% and 408%), respectively, when compared to the control group. Pleural exudate from LDTI-2PL and BmTIs plus carrageenan-treated rats showed a significant increase in plasma kallikrein-like activity, measured by chromogenic substrate hydrolysis. The specific inhibition of enzymatic activity with aprotinin confirmed that 50% of S2302 hydrolysis was produced by plasma kallikrein-like enzymes. Kinin release was increased by 97% and 103% in exudates from LDTI-2PL and BmTIs plus carrageenan-treated rats, respectively. Considering that the plasmin inhibitors LDTI-2PL and BmTIs increased exudation, leukocyte migration and bradykinin release, our results suggest an anti-inflammatory role for plasmin in the pleurisy model.