Adrenomedullin suppresses fMLP-induced upregulation of CD11b of human neutrophils.
In this study we investigated the effect of adrenomedullin (AM) on fMLP-mediated activation of human neutrophils. AM partially, but significantly, suppressed fMLP-induced upregulation of CD11b expression. The inhibitory effects of AM upon fMLP-induced upregulation of CD11b expression were completely blocked by CGRP [8-37], a CGRP receptor antagonist. AM significantly increased cAMP content in neutrophils and SQ-22,536, an adenylate cyclase inhibitor, and KT-5720, a PKA inhibitor, significantly blocked the inhibitory effects of AM upon fMLP-induced upregulation of CD11b expression. This study indicates that binding of AM to the CGRP receptor suppresses fMLP-induced upregulation of CD11b expression of human neutrophils by increasing intracellular cAMP levels. AM may play an important role in the regulation of inflammatory processes, especially in the binding of neutrophils to vascular endothelial cells and subsequent neutrophil emigration evident in acute pulmonary inflammation.
Saito
Y
Y
Division of Respiratory Medicine and Allergy, Fujita Health University School of Medicine, Toyoake-city, Aichi, Japan.
Nakagawa
C
C
Uchida
H
H
Sasaki
F
F
Sakakibara
H
H
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D000067956:Adenylyl Cyclase Inhibitors; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004791:Enzyme Inhibitors; D016177:Macrophage-1 Antigen; D010446:Peptide Fragments; D010455:Peptides; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; C017759:9-(tetrahydro-2-furyl)-adenine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000225:Adenine; D015740:Calcitonin Gene-Related Peptide