title: Lysophosphatidylcholines prime the NADPH oxidase and stimulate multiple neutrophil functions through changes in cytosolic calcium.
abstract: A mixture of lysophosphatidylcholines (lyso-PCs) are generated during blood storage and are etiologic in models of acute lung injury. We hypothesize that lyso-PCs stimulate polymorphonuclear neutrophils (PMNs) through Ca(2)(+)-dependent signaling. The lyso-PC mix (0.45-14.5 micro M) and the individual lyso-PCs primed formyl-Met-Leu-Phe (fMLP) activation of the oxidase (1.8- to 15.7-fold and 1.7- to 14.8-fold; P<0.05). Labeled lyso-PCs demonstrated a membrane association with PMNs and caused rapid increases in cytosolic Ca(2)(+). Receptor desensitization studies implicated a common receptor or a family of receptors for the observed lyso-PC-mediated changes in PMN priming, and cytosolic Ca(2)(+) functions were pertussis toxin-sensitive. Lyso-PCs caused rapid serine phosphorylation of a 68-kD protein but did not activate mitogen-activated protein kinases or cause changes in tyrosine phosphorylation. With respect to alterations in PMN function, lyso-PCs caused PMN adherence, increased expression of CD11b and the fMLP receptor, reduced chemotaxis, provoked changes in morphology, elicited degranulation, and augmented fMLP-induced azurophilic degranulation (P<0.05). Cytosolic Ca(2)(+) chelation inhibited lyso-PC-mediated priming of the oxidase, CD11b surface expression, changes in PMN morphology, and serine phosphorylation of the 68-kD protein. In conclusion, lyso-PCs affect multiple PMN functions in a Ca(2)(+)-dependent manner that involves the activation of a pertussis toxin-sensitive G-protein.
authors.affiliation: Bonfils Blood Center, Denver, Colorado 80230, USA. Christopher.Silliman@uchsc.edu
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
authors.forename: David J
authors.initials: DJ
authors.lastname: Elzi
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Ambruso
authors.forename: Rene J
authors.initials: RJ
authors.lastname: Musters
authors.forename: Christine
authors.initials: C
authors.lastname: Hamiel
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Harbeck
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Paterson
authors.forename: A Jason
authors.initials: AJ
authors.lastname: Bjornsen
authors.forename: Travis H
authors.initials: TH
authors.lastname: Wyman
authors.forename: Marguerite
authors.initials: M
authors.lastname: Kelher
authors.forename: Kelly M
authors.initials: KM
authors.lastname: England
authors.forename: Nathan
authors.initials: N
authors.lastname: McLaughlin-Malaxecheberria
authors.forename: Carlton C
authors.initials: CC
authors.lastname: Barnett
authors.forename: Junichi
authors.initials: J
authors.lastname: Aiboshi
authors.forename: Anirban
authors.initials: A
authors.lastname: Bannerjee
mesh_terms: D018845:CD11 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002448:Cell Adhesion / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003600:Cytosol; D004789:Enzyme Activation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007781:Lactoferrin / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010196:Pancreatic Elastase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D018845:CD11 Antigens; D036341:Intercellular Signaling Peptides and Proteins; D008244:Lysophosphatidylcholines; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C039351:platelet activating factor receptor; D014443:Tyrosine; D012694:Serine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D019255:NADPH Oxidases; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; D007781:Lactoferrin; D010196:Pancreatic Elastase; D002118:Calcium