Inhibition of leukocyte chemotaxis by Glu-Glu-Glu-Glu-Tyr-Pro-Met-Glu and Leu-Ile-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-Arg-Gln-Gly.
Chemotaxis of rabbit peritoneal leucocytes stimulated by fMet-Leu-Phe, a synthetic chemoattractant, was inhibited by Glu-Glu-Glu-Glu-Tyr-Pro-Met-Glu (MT peptide) and Leu-Ile-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-Arg-Glu-Gly (Src peptide). Both peptides did not inhibit the binding of [3H] formyl-NLe-Leu-Phe, a chemoattractant, to neutrophils, suggesting that the peptides inhibit the events distal to the chemotactic receptors. These peptides blocked the release of arachidonic acid from phospholipids in neutrophils stimulated with chemoattractants, whereas they had no effect on phospholipase A2 activity itself. The peptides markedly reduced the phosphorylation of lipomodulin, a phospholipase inhibitory protein, in either intact cells or isolated plasma membranes. Lipomodulin immunoprecipitated by monoclonal anti-lipomodulin antibody had phosphorylserine and phosphoryltyrosine as analyzed upon electrophoresis. The MT peptide which does not contain threonine or serine was phosphorylated by isolated plasma membranes. These results, taken together, suggest that a tyrosine phosphorylating kinase is involved in biochemical events of chemotactic receptors, and that lipomodulin is a substrate for this kinase.
D000818:Animals; D017302:Annexins; D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006023:Glycoproteins; D007700:Kinetics; D008222:Lymphokines / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship
D017302:Annexins; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D008222:Lymphokines; C040474:MT Peptide; D009842:Oligopeptides; D011506:Proteins; C040475:Src peptide; C030958:lipomodulin; D009240:N-Formylmethionine Leucyl-Phenylalanine