Inhibition of neutrophil-mediated degradation of isolated basement membrane collagen by nonsteroidal antiinflammatory drugs that inhibit degranulation.

The ability of nonsteroidal antiinflammatory drugs to inhibit neutrophil-mediated degradation of type IV collagen in an in vitro tissue injury model using glomerular basement membrane (GBM) containing immune complexes was investigated. Auranofin (2.5-10 microM), phenylbutazone (50-250 microM), sulfasalazine (250-1,000 microM), and 4-bromophenacyl bromide (5-20 microM) each inhibited up to 70% of the collagen degradation, in parallel with almost complete inhibition of the release of azurophil and specific granule enzymes. These drugs had much less an effect on gelatinase release. Indomethacin and the antimalarials, which inhibited the neutrophil oxidative burst but not degranulation, had little effect on GBM collagen degradation. Our results do not necessarily imply that inhibition of neutrophil-mediated degradation of connective tissue is relevant to the action of nonsteroidal antiinflammatory drugs in vivo; however, using the GBM model system, we have shown that when a drug inhibits granule enzyme release, there is an associated decrease in collagen degradation, whereas inhibition of the oxidative burst has relatively little effect.