Tumor necrosis factor-alpha regulates expression of receptors for formyl-methionyl-leucyl-phenylalanine, leukotriene B4, and platelet-activating factor. Dissociation from priming in human polymorphonuclear neutrophils.
TNF-alpha enhances polymorphonuclear responses to many stimuli, including chemotactic peptide FMLP. It also promotes expression of FMLP receptors and thus may prime polymorphonuclear neutrophils to this and other agonists by up-regulating signal recognition molecules. However, we find that the cytokine's actions on FMLP receptors lagged priming of FMLP-induced degranulation. Moreover, TNF-alpha enhanced degranulation responses to leukotriene B4 and platelet-activating factor but paradoxically down-regulated leukotriene B4 receptors and only transiently up-regulated platelet-activating factor receptors. Hence, TNF-alpha has pleiotropic effects on receptor expression; these effects diverge from priming; and a large part of the primed state must reflect enhancement of post-receptor events.
O'Flaherty
J T
JT
Department of Medicine, Wake Forest University Medical School, Winston-Salem, NC 27106.
Rossi
A G
AG
Redman
J F
JF
Jacobson
D P
DP
D015550:Cell Degranulation; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000378:metabolism; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic / Q000378:metabolism*; D018102:Receptors, Leukotriene B4; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009113:Muramidase