Secretion of Collagenolytic Enzymes by Human Polymorphonuclear Leukocytes

Abstract

The polymorphonuclear leukocyte contains three proteinases capable of degrading the collagenous components of the connective tissue matrix. These proteinases, gelatinase, interstitial collagenase and elastase, were found to be rapidly secreted by the neutrophil in response to soluble stimuli with maximal accumulation of the gelatinase and interstitial collagenase occurring during a 20 minute incubation. When neutrophils were stimulated with the chemotactic peptide, formyl-met-leu-phe, gelatinase was the predominant collagenolytic enzyme detected. Stimulation of neutrophils with increasing doses of the Ca++ ionophore A23187 lead to a sequential release of collagenolytic proteinases. Gelatinase release was detected at Ca++ ionophore concentrations of .05-.1 μM, while significant release of interstitial collagenase required 0.5-1 μM A23187. Elastolytic activity was detected only at high concentrations of A23187 (5-10 μM). No release of lactic acid dehydrogenase was detected indicating that the enzyme release was not due to cell death. These studies suggest that the neutrophil may modulate its collagenolytic potential by selective release of collagenolytic proteinases.