Oxidized N-formylmethionyl-leucyl-phenylalanine: effect on the activation of human monocyte and neutrophil chemotaxis and superoxide production.
F-met-leu-phe, a potent neutrophil and monocyte chemoattractant, can be oxidized to F-met-leu-phe sulfoxide by metabolically activated neutrophils. We investigated the interaction of human neutrophils and monocytes with chemically prepared oxidized derivatives of F-met-leu-phe: F-met-leu-phe sulfoxide and F-met-leu-phe sulfone. We compared the derivatives with nonoxidized parent F-met-leu-phe for specific binding to neutrophils and monocytes, and for effectiveness as chemoattractants and stimuli of superoxide production. We observed that neutrophils did not migrate to either derivative over the concentration range of 10(-9) to 10(-3) M. In marked contrast, monocytes migrated to both oxidized peptides, with optimal chemotaxis occurring at derivative concentrations 10- to 100-fold higher than the optimal parent F-met-leu-phe concentration. F-met-leu-phe sulfoxide and sulfone stimulated neutrophil and monocyte superoxide production and specifically bound to both neutrophils and monocytes at optimal concentrations that were 10- to 100-fold greater than the optimal parent F-met-leu-phe concentration. These results suggest that the higher concentrations of oxidized derivatives required for monocyte migration and for neutrophil and monocyte superoxide production are due to a reduced affinity of the oxidized derivatives for the F-met-leu-phe receptor. The finding that oxidized F-met-leu-phe binds to the neutrophil receptor without eliciting a chemotactic response suggests that the F-met-leu-phe receptor complex or chemotaxis transduction mechanism is different in human neutrophils and monocytes.
D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis; D044042:Receptors, Formyl Peptide; D013481:Superoxides / Q000378:metabolism*
D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C036773:N-formylmethionyl sulfoxide-leucyl-phenylalanine