The cell biology of leukocyte-mediated proteolysis

Abstract

Leukocyte-derived proteinases have the capacity to degrade every component of the extracellular matrix, and thereby play fundamental roles in physiological processes. However, if the activity of these proteinases is uncontrolled or dysregulated, they have the capacity to contribute to tissue injury that potentially affects every organ in the body. Although there is a substantial literature on structure and activity of these proteinases when they are free in solution, until recently there has been little information about the cell biology of proteinases and their inhibitors. Recent studies, however, have identified several mechanisms by which inflammatory cells can degrade extracellular proteins in a milieu that contains high-affinity proteinase inhibitors. J. Leukoc. Biol. 65: 137-150; 1999.

Polymorphonuclear proteolytic activity and milk composition change

“…After LPS infusion, the capacity of caseinolysis of PMN neutral proteases and acidic proteases has been shown by Moussaoui et al [50]. PMN are reported to contain acidic proteases such as cathepsins B, C, D or L [54]. These proteases are not at their optimal pH after degranulation since they are in the environment (milk) with a pH tending to neutrality, suggesting that neutral proteases cannot degrade proteins in an extra-cellular way.…”

“…During the inflammatory response, the activities of these proteases are significantly increased as reported for collagenase [60], elastase [5,60], cathepsin G only [5] and both cathepsins C and G [60]. The role of these proteases in the degradation of the extracellular matrix is well known [5,54]. Many studies report a high SCC during mastitis with mainly PMN [31].…”

“…[31,54]. After LPS infusion, the capacity of caseinolysis of PMN neutral proteases and acidic proteases has been shown by Moussaoui et al [50].…”

“…PMN proteases degrade other proteins of the extracellular matrix such as collagen, gelatins, laminin, etc. [54].…”

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“…It has been suggested that the increased capillary permeability at inflammatory foci allows SSL to extravasate (14). Besides, the infiltration of inflammatory cells may actively or passively promote SSL localization, either by taking up liposomes in the circulation and subsequent infiltration into the inflamed tissue, or by facilitating liposome extravasation as a result of leukocyte-mediated tissue inury (16).…”