Modulation of beta2 integrin phenotype, adhesion, chemotaxis, and oxidative burst of neutrophils by cyclosporine.
Cyclosporine (CsA) is an immunosuppressive drug widely used to prevent allograft rejection, but its action on neutrophil function is not well known. Neutrophils play an important role in tissue damage during allograft rejection; chemotactic recruitment, adhesion to endothelial cells and oxidative burst of neutrophils are early events during allograft rejection. The aim of this work was to evaluate the effect of CsA on beta2 integrins' surface expression, adhesion to human umbilical endothelial cells (HUVECs), chemotaxis and oxidative burst by neutrophils. For any neutrophil function studied, data obtained from activated neutrophils exposed to CsA were compared with those derived from untreated controls. Results show that CsA does not block neutrophil chemotaxis and does not reduce surface expression of CD11 complex and HUVECs' adhesion at all concentrations tested (15, 100 and 500 ng/mL) and at incubation times of 1, 2 and 4 h as compared to controls. On the other hand, the drug affects significantly the CD18 phenotype after two hours of treatment at the maximum concentration (500 ng/mL) (P < 0.05; ANOVA) and the oxidative burst after four hours (P < 0.01; ANOVA). This study provides evidence that in addition to the well-known CsA effects on lymphocyte functions, the drug affects some neutrophil functions with dose- and time-dependent modalities.
Dept. Internal Medicine, S. Chiara Hospital, Pisa, Italy.
M
M
Scavuzzo
A
A
Sagripanti
F
F
Mosca
F
F
Ambrogi
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics*; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects*; D010641:Phenotype; D016897:Respiratory Burst / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine