Inhibitory action of synthetic proteinase inhibitors and substrates on the chemotaxis of rat polymorphonuclear leukocytes in vitro.

The effect of synthetic proteinase inhibitors (PIs) and proteinase substrates on chemotaxis of rat polymorphonuclear leukocytes (PMNs) was studied by using Boyden's method in vitro. Serine-PIs had a potent inhibitory activity on PMN chemotaxis. The relative potencies of the inhibitory action of PIs on the PMN chemotaxis in vitro were TPCK greater than inhibitor B greater than or equal to TLCK greater than EACA hexyl ester greater than FR 45009. The experiments using serine-proteinase substrates suggest an important role of chymotrypsin-like proteinase of PMNs in the process of PMN chemotaxis. Leupeptin had no direct effect on PMN chemotaxis in vitro, but significantly suppressed the zymosan-mediated generation of a chemoattractant for PMNs in rat serum. Other PIs had no effect on the generation of PMN chemoattractant. These results suggest that the PIs except leupeptin suppress PMN infiltration in vivo as a result of a direct action on PMNs, while leupeptin indirectly suppresses PMN infiltration in vivo through the inhibition of the generation of a chemoattractant for PMNs.