Role of p38 in the Priming of Human Neutrophils by Peritoneal Dialysis Effluent

AUTOR(ES)

Daniels, Ian

FONTE

American Society for Microbiology

RESUMO

Peritoneal dialysis effluent (PDE) contains a low-molecular-weight substance that is able to prime human neutrophils for the release of arachidonic acid and superoxide anion. Conventional priming agents, such as tumor necrosis factor alpha (TNF-α), are known to signal via mitogen-activated protein (MAP) kinases; at least one possible substrate for MAP kinases is cytosolic phospholipase A2 (cPLA2). Phosphorylation of this enzyme results in arachidonic acid release, and this fatty acid is a potent primer and activator of the human neutrophil NADPH oxidase. Because of the striking similarities between the priming of neutrophils with agents such as TNF-α and PDE, we have investigated the signalling pathways evoked by PDE and explored the possibility that cPLA2 is a target for activated MAP kinases. Our results show that PDE treatment of human neutrophils results in the phosphorylation of the p38 kinase rather than the p42 and p44 kinases. Phosphorylation of p38 is transient with maximal activity being observed 1 min after exposure to PDE. We were unable to demonstrate that activation of p38 resulted in phosphorylation of cPLA2; furthermore, translocation of this enzyme to a membrane-containing fraction was not enhanced in PDE-treated neutrophils. Taken together, these data suggest that, in a manner similar to that of TNF-α, PDE primes human neutrophils by the activation of the p38 kinase. However, unlike the cytokine, the activation of this protein does not result in phosphorylation or activation of cPLA2.

Documentos Relacionados

• Role of Arachidonic Acid and Its Metabolites in the Priming of NADPH Oxidase in Human Polymorphonuclear Leukocytes by Peritoneal Dialysis Effluent
• Lipopolysaccharide-Binding Protein- and CD14-Dependent Activation of Mitogen-Activated Protein Kinase p38 by Lipopolysaccharide in Human Neutrophils Is Associated with Priming of Respiratory Burst
• Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride
• Activation of the Mitogen-Activated Protein Kinase p38 by Human Cytomegalovirus Infection through Two Distinct Pathways: a Novel Mechanism for Activation of p38
• Hydrogen peroxide generation by polymorphonuclear leukocytes exposed to peritoneal dialysis effluent.