Adiponectin inhibits neutrophil phagocytosis of Escherichia coli by inhibition of PKB and ERK 1/2 MAPK signalling and Mac-1 activation.
Full length adiponectin is a potent immune modulatory adipokine, impacting upon the actions of several immune cells. Neutrophil oxidative burst has been shown to decrease in response to adiponectin, and we speculated that it could have other effects on neutrophil function. Here we report that adiponectin reduces the phagocytic ability of human neutrophils, decreasing significantly the ingestion of opsonised E. coli by these cells in whole blood (p<0.05) and as isolated neutrophils (p<0.05). We then determined the mechanisms involved. We observed that the activation of Mac-1, the receptor engaged in complement-mediated phagocytosis, was decreased by adiponectin in response to E. coli stimulation. Moreover, treatment of neutrophils with adiponectin prior to incubation with E. coli significantly inhibited signalling through the PI3K/PKB and ERK 1/2 pathways, with a parallel reduction of F-actin content. Studies with pharmacological inhibitors showed that inhibition of PI3K/PKB, but not ERK 1/2 signalling was able to prevent the activation of Mac-1. In conclusion, we propose that adiponectin negatively affects neutrophil phagocytosis, reducing the uptake of E. coli and inhibiting Mac-1 activation, the latter by blockade of the PI3K/PKB signal pathway.
Medical Research Council Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom.
Alessandra
A
Rossi
Janet
J
Lord
D052242:Adiponectin / Q000494:pharmacology; D001323:Autoantibodies / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D016177:Macrophage-1 Antigen / Q000235:genetics* / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009895:Opsonin Proteins / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
C499918:ADIPOQ protein, human; D052242:Adiponectin; D001323:Autoantibodies; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D011994:Recombinant Proteins; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3