title: Leukocyte inhibitory factor (LIF) potentiates neutrophil responses to formyl-methionyl-leucyl-phenylalanine.
abstract: The ability of purified (80,000-fold) human leukocyte inhibitory factor (LIF) to modulate several formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe)-induced neutrophil functions was evaluated. Although not affecting directed migration itself, at low concentrations (1/2 to 2 U/ml), LIF was demonstrated to potentiate chemotaxis induced by f-met-leu-phe (40.3% +/- 8.1) and to reduce the concentration of f-met-leu-phe necessary for maximal chemotaxis (10(-8) to 10(-9) M). Similarly, LIF did not directly induce the respiratory burst, but potentiated both superoxide generation (151.6% +/- 77) and hydrogen peroxide production (54.9% +/- 15.5) in the presence of f-met-leu-phe (10(-7) M). LIF was also shown to induce degranulation of neutrophil-specific granules in a dose-dependent manner. Neutrophil-specific granules have been shown to contain an intracellular pool of receptors for f-met-leu-phe, and on degranulation provide the surface membrane with a fresh source of receptors. Our data suggested that LIF potentiation of neutrophil stimulation by f-met-leu-phe might be mediated, at least in part, by increasing the number of available membrane receptors as a result of its ability to induce degranulation. Radioligand receptor analysis using f-met-leu-[3H] phe was performed, and LIF was shown to mediate an increase in receptors for f-met-leu-phe from an average of 18,600 on untreated cells to 27,000 after pretreatment with LIF. This increase in receptors could "sensitize" the neutrophils for f-met-leu-phe and possibly explain the potentiation of neutrophil stimulation observed in the presence of the ligand. LIF was also found to have a more generalized effect on the transduction of neutrophil activation stimuli, mediating a 35.8% increase in superoxide production after exposure to calcium ionophore. The data do not permit a determination as to whether the increase in receptor number is responsible for the potentiation of f-met-leu-phe-mediated function, or whether this occurs secondary to the more generalized effect on neutrophil stimulation transduction.
mesh_terms: D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008222:Lymphokines / Q000276:immunology* / Q000302:isolation & purification; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010101:Oxygen Consumption / Q000187:drug effects; D011869:Radioligand Assay; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology
chemical_list: D003574:Cytochrome c Group; D008222:Lymphokines; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; C010598:leukocyte inhibitory factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide