Abstract
We studied the effects and mechanisms of activated rabbit peritoneal neutrophils (PMN) on endothelial-bound angiotensin converting enzyme (ACE) activity in cultured bovine pulmonary arterial endothelial cells (EC), using [3H]-Benzoyl-Phe-Ala-Pro as the ACE substrate under first order reaction condition. Phorbol myristate acetate (PMA) or PMN alone had no effects on ACE activity. When PMN were co-incubated (activated) with PMA (10 ng/ml) for 4 hours in Earle’s salt solution, endothelial ACE activity was decreased 87%. No EC cytotoxicity was noticed at this stage as determined by 51Cr release fromre-labelled EC. PMN-mediated ACE dysfunction was inhibited by catalase (2,000 U/ml), but not by superoxide dismutase (300 U/ml). PMN-mediated ACE dysfunction was also inhibited by the hydroxyl radical scavenger dimethyl thiourea (5 mM) but not mannitol (5 mM), which does not cross the cell membrane. Pre-treatment of EC with the iron chelator deferoxamine mesylate (1 to 10 mM) for 4 h attenuated the PMN-mediated ACE dysfunction, while co-incubation deferoxamine did not affect the activated PMN-mediated ACE dysfunction. The thiol reducing agent, 2-mercaptoethanol (0.1 mM) alsop revented PMN-mediated ACE dysfunction. The myeloperoxidase inhibitor, cyanide (5 mM), but not azide (1 to 50 mM), also inhibited the activated PMN-induced EC ACE dysfunction. Treatment with the proteinase inhibitor phenylmethylsulfonyl fluoride or with human a-antitrypsin did not affect the action of activated PMN. NO synthase inhibitor, Nw-nitro-L-arginine (0.1 mM), also had no effects on PMN-mediated ACE dysfunction. These results suggest that PMN-mediated ACE dysfunction may be due to the production of hydrogen peroxide by PMN and its conversion into hydroxyl radicals.
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© 1993 Springer Science+Business Media New York
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Chen, X., Catravas, J.D. (1993). PMA-Activated Neutrophil-Mediated Endothelial Angiotensin Converting Ectoenzyme Dysfunction. In: Catravas, J.D., Callow, A.D., Ryan, U.S. (eds) Vascular Endothelium. NATO ASI Series, vol 257. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2437-3_19
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DOI: https://doi.org/10.1007/978-1-4615-2437-3_19
Publisher Name: Springer, Boston, MA
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