Leukotriene B 4 and its action with a free-radical-generating system

Abstract

The concentration of Leukotriene B 4 (LTB 4) demonstrated in early inflammation has been shown to induce leukocyte aggregation, chemotaxis and degranulation of polymorphonuclear leukocytes (PMN) in vitro . N-f-Met. Leu-Phe, a potent chemotactic factor, has been shown to activate neutrophils to produce chemiluminescence and produce superoxide radicals. The characteristics of the LTB 4-induced degranulation of rabbit neutrophils are strikingly similar to those of the chemotactic factors. Thiols, and in partiicular glutathione, have been shown to have a marked inhibitory effect in clinical assays of superoxide dismutase (SOD) activity, using reactions which are supposedly specific for the superoxide ion. SOD is most frequently assessed by coupling a generator of O 2 − with an indicating scavenger for the radical. The enzyme then competes with the scavenger for the available O 2 − and inhibits the processes being observed, thus, the inhibition serves as a basis for estimation of SOD activity. A method proposed by Misra and Fridovich for the estimation of SOD activity is based on the photo-oxidation of dianisidine sensitised by riboflavin. This assay can be used to classify compounds as either SOD-like or glutathione-like. With a small quantity if LTB 4 and LTD 4, we obtained preliminary results for their effect on the assay (Table 1). They appear to be glutathione-like, i.e., reactive with the free-radical-generating system in preference to a specific reaction with O 2 − and are only slightly less effective than glutathione. Although our results are preliminary it is clear that the leukotrienes are effective as radical scavengers in this reaction. Further studies with two prostaglandis (products of the cycloxygenase pathway) will also be presented.