Effect of immunosuppressive drugs on the release of metalloproteinases from human polymorphonuclear leukocytes

Abstract

The concentration of the metalloproteinases type I collagenase and gelatinase was measured in isolated polymorphonuclear leukocytes (PMNLs) of renal transplant recipients treated either with cyclosporin A (CyA) and prednisolone (Pr) (n = 8) or azathioprine (Aza) and Pr (n = 8), and of healthy subjects (n = 12). PMNLs of CyA- and Aza-treated transplant patients displayed markedly higher gelatinase content (2427 +/- 489 and 3284 +/- 357 ng/10(7) cells) than PMNLs of controls (528 +/- 83 ng/10(7) cells). There was also a higher content of type I collagenase in PMNLs (3374 +/- 292 ng/10(7) cells) of Aza-treated patients and significantly elevated levels in PMNLs of patients receiving CyA (3625 +/- 229 ng/10(7) cells) compared with healthy subjects (2878 +/- 151 ng/10(7) cells). In contrast, neutrophil lactoferrin content was lower in transplant patients. Thus, immunosuppressive drugs may reduce the release of leukocyte proteinases, which are known for their deleterious role in proteolytic tissue and matrix breakdown. In vitro, the effects of different immunosuppressive drugs on the release of lactoferrin, collagenase and gelatinase were investigated on FMLPNTL-stimulated PMNLs isolated from healthy subjects. CyA but not Aza or Pr caused inhibition of gelatinase, collagenase and lactoferrin release.