title: Pulmonary endothelial cell killing by human neutrophils. Possible involvement of hydroxyl radical.
abstract: Human blood neutrophils stimulated by a variety of agents were shown to have cytotoxic effects on bovine pulmonary artery endothelial cells. Effective agonists included immune complexes, opsonized zymosan and 12-O-tetradecanoyl phorbol acetate. Unstimulated human neutrophils and neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine or with platelet-activating factor failed to induce significant killing even though secretory release of lysosomal enzymes occurred. In comparing the effects of the different agonists, endothelial cell killing showed a better correlation with the production of H2O2 than with the generation of O2-. Endothelial cell killing by stimulated human neutrophils was inhibited by catalase but not by soybean trypsin inhibitor or superoxide dismutase. Killing was also inhibited by two scavengers (N, N-dimethylthiourea and D-mannitol) of hydroxyl radical and by deferoxamine mesylate, an iron-chelator. Iron-saturated deferoxamine mesylate was significantly less effective in protecting the endothelial cells against killing. Agents that were protective against endothelial cell killing did not interfere with the generation of O2- in stimulated neutrophils. These results suggest that leukocyte-induced endothelial cell killing in vitro can be induced by some but not all agonists for neutrophils and that the killing is oxygen-dependent and may be directly due to hydroxyl radical production.
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004727:Endothelium / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology
chemical_list: D006878:Hydroxides; D017665:Hydroxyl Radical; D010447:Peptide Hydrolases