SUBLETHAL DOSES OF EXOGENOUS HYDROGEN-PEROXIDE PRIME HUMAN NEUTROPHILS TO FORMYL PEPTIDE

Hydrogen peroxide (H2O2) is an oxidative agent important in inflammati on and ischemia. Neutrophils (PMNs) are a main source of H2O2 in the i nflammatory focus. However, after recruitment into the inflammatory or ischemic zone of the heart, the PMN itself might serve as a target fo r exogenous H2O2. In the present work we found that PMNs are very resi stant to the cytotoxic action of H2O2 (LD50 for PMNs is about 30-50 mM , whereas for endothelial cells it is about 200-300 muM). Unexpectedly , treatment of PMNs by H2O2 at a sublethal dose of 10 mM leads to a su bsequent increase in the generation of superoxide anion in response to the chemoattractant peptide FMLP (twofold increase in O2- generation 30 min after treatment by H2O2 as compared with nontreated control cel ls). H2O2 itself does not induce O2- generation by PMNs. Therefore, an y H2O2 that accumulated in the inflammatory or ischemic zone might alt er the functional activity of PMNs and prime them to subsequent agonis t activation.