Activation of latent polymorphonuclear leucocyte collagenase by the glutathione cycle

The intrapleural injection of carrageenin into rats caused accumulation of leucocytes in the pleural cavity and changes in blood leucocyte populations. An increased number of polymorphonuclear (PMN) leucocytes was observed. The peripheral blood PMN leucocytes of untreated rats contained 33.2 nM reduced glutathione/10(7) cells and collagenase mainly in the latent form. During experimental pleurisy in blood leucocytes as well as in the leucocytes obtained from the pleural exudate, the level of reduced glutathione decreased significantly by about 33% (22.4 nM/10(7) cells) and parallel collagenase activation up to 80-100% was observed. Two tested antiinflammatory drugs, Timegadine and piroxicam, which significantly inhibited activation of latent collagenase during the course of inflammation and partially protected reduced glutathione against oxidation. These results suggest that the activation of latent leucocyte collagenase in vivo via the disulphide-thiol interchange reaction may be coupled to the glutathione cycle and regulated by variation in its redox potential.