Phagocyte activation by Trp-Lys-Tyr-Met-Val-Met, acting through FPRL1/LXA4R, is not affected by lipoxin A4.
Lipoxin A4 (LXA4) has been shown to bind to the leucocyte formyl peptide receptor (FPR) homologue, FPRL1, without triggering the biological activities induced by other FPRL1 agonists. We investigated the direct effect of LXA4 as well as the effect on agonist-induced biological responses using transfected HL-60 cells expressing FPR, FPRL1 or FPRL2. LXA4 neither induced an intracellular rise in calcium in these transfectants nor affected the response induced by the peptide Trp-Lys-Tyr-Met-Val-Met (WKYMVM), an agonist that activates cells through FPRL1 and -2. Both agonists induced Erk-2 activation; however, the eicosanoid-induced activity was independent of FPRL1 and FPRL2. Moreover, LXA4 was unable to trigger neutrophil upregulation of complement receptor 3 and respiratory burst, and it had no effect on the responses induced by triggering with WKYMVM. We conclude that LXA4 is unable to affect the WKYMVM-induced signalling through FPRL1 and suggest that it acts through a receptor different from FPRL1.
Christophe
T
T
DRCD/BBSI (UMR 5092, CEA/CNRS/UJF), Grenoble, Cedex, France.
Karlsson
A
A
Rabiet
M-J
MJ
Boulay
F
F
Dahlgren
C
C
D020013:Calcium Signaling / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D044045:Lipoxins; D016177:Macrophage-1 Antigen / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019255:NADPH Oxidases / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000235:genetics / Q000276:immunology*; D014162:Transfection
C105101:FPR2 protein, human; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D016177:Macrophage-1 Antigen; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide; C113617:Trp-Lys-Tyr-Met-Val-Met; C040527:lipoxin A4; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases