Biomaterial Database

Oxidized N-formylmethionyl-leucyl-phenylalanine: effect on the activation of human monocyte and neutrophil chemotaxis and superoxide production. 1984

L Harvath, and R R Aksamit

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.

UI	MeSH Term	Description	Entries
D008262	Macrophage Activation	The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.	Activation, Macrophage,Activations, Macrophage,Macrophage Activations
D009000	Monocytes	Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.	Monocyte
D009240	N-Formylmethionine Leucyl-Phenylalanine	A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.	F-Met-Leu-Phe,N-Formyl-Methionyl-Leucyl-Phenylalanine,Formylmet-Leu-Phe,Formylmethionyl Peptide,Formylmethionyl-Leucyl-Phenylalanine,Formylmethionylleucylphenylalanine,N-Formylated Peptide,N-formylmethionyl-leucyl-phenylalanine,fMet-Leu-Phe,F Met Leu Phe,Formylmet Leu Phe,Formylmethionyl Leucyl Phenylalanine,Leucyl-Phenylalanine, N-Formylmethionine,N Formyl Methionyl Leucyl Phenylalanine,N Formylated Peptide,N Formylmethionine Leucyl Phenylalanine,N formylmethionyl leucyl phenylalanine,Peptide, Formylmethionyl,Peptide, N-Formylated,fMet Leu Phe
D009504	Neutrophils	Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.	LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002634	Chemotaxis, Leukocyte	The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.	Leukotaxis,Leukocyte Chemotaxis
D004306	Dose-Response Relationship, Immunologic	A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.	Immunologic Dose-Response Relationship,Relationship, Immunologic Dose-Response,Dose Response Relationship, Immunologic,Dose-Response Relationships, Immunologic,Immunologic Dose Response Relationship,Immunologic Dose-Response Relationships,Relationship, Immunologic Dose Response,Relationships, Immunologic Dose-Response
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013481	Superoxides	Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.	Superoxide Radical,Superoxide,Superoxide Anion
D044042	Receptors, Formyl Peptide	A family of G-protein-coupled receptors that was originally identified by its ability to bind N-formyl peptides such as N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE. Since N-formyl peptides are found in MITOCHONDRIA and BACTERIA, this class of receptors is believed to play a role in mediating cellular responses to cellular damage and bacterial invasion. However, non-formylated peptide ligands have also been found for this receptor class.	Chemotactic Peptide Receptor,Chemoattractant Receptor,F-Chemotactic Peptide Receptor,FMLP Receptor,Formyl Peptide Receptor,N-Formylmethionyl Peptide Receptor,N-formyl Hexapeptide Receptor,Receptor, Chemotactic Peptide,fMet-Leu-Phe Receptor,F Chemotactic Peptide Receptor,Formyl Peptide Receptors,Hexapeptide Receptor, N-formyl,N Formylmethionyl Peptide Receptor,N formyl Hexapeptide Receptor,Peptide Receptor, Chemotactic,Peptide Receptor, N-Formylmethionyl,Peptide Receptors, Formyl,Receptor, Chemoattractant,Receptor, F-Chemotactic Peptide,Receptor, FMLP,Receptor, Formyl Peptide,Receptor, N-Formylmethionyl Peptide,Receptor, N-formyl Hexapeptide,Receptor, fMet-Leu-Phe,fMet Leu Phe Receptor