Effects of nitric oxide on the eosinophil survival in vitro. A role for nitrosyl-heme

In a previous paper we showed that the nitric oxide (NO) donors azide and h ydroxylamine inhibited eosinophil apoptosis, Azide and hydroxylamine genera te a nitrosyl-heme complex - due to endogenous catalase activity - which ac tivates soluble guanylate cyclase. In contrast, in the present paper, we sh ow that NO donors (SNAP, SIN-1, S-nitroso-L-cysteine, NOC-18) which spontan eously release NO in physiological solutions did not support the survival o f eosinophils and induced apoptosis or necrosis. However, the addition of h ematin (the ferric form of heme) together with low doses of NO (SNAP 10 mu M) promoted eosinophil survival. In conclusion, we propose that NO and heme (e.g. from heme-containing enzymes such as peroxidase or catalase), both r eleased in inflammation sites, could form nitrosyl-heme and thus promote eo sinophilic inflammation. (C) 1999 Federation of European Biochemical Societ ies.