Adrenomedullin suppresses fMLP-induced upregulation of CD11b of human neutrophils

Y Saito; C Nakagawa; H Uchida; F Sasaki; H Sakakibara

doi:10.1023/a:1011092532100

Adrenomedullin suppresses fMLP-induced upregulation of CD11b of human neutrophils

Inflammation. 2001 Jun;25(3):197-201. doi: 10.1023/a:1011092532100.

Authors

Y Saito¹, C Nakagawa, H Uchida, F Sasaki, H Sakakibara

Affiliation

¹ Division of Respiratory Medicine and Allergy, Fujita Health University School of Medicine, Toyoake-city, Aichi, Japan.

PMID: 11403211
DOI: 10.1023/a:1011092532100

Abstract

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.

MeSH terms

Adenine / analogs & derivatives*
Adenine / pharmacology
Adenylyl Cyclase Inhibitors
Adrenomedullin
Calcitonin Gene-Related Peptide / pharmacology
Calcitonin Gene-Related Peptide Receptor Antagonists
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Drug Interactions
Enzyme Inhibitors / pharmacology
Humans
In Vitro Techniques
Inflammation / etiology
Macrophage-1 Antigen / metabolism*
N-Formylmethionine Leucyl-Phenylalanine / pharmacology*
Neutrophils / drug effects*
Neutrophils / immunology*
Neutrophils / metabolism
Peptide Fragments / pharmacology
Peptides / pharmacology*
Peptides / physiology
Up-Regulation / drug effects

Substances

Adenylyl Cyclase Inhibitors
Calcitonin Gene-Related Peptide Receptor Antagonists
Enzyme Inhibitors
Macrophage-1 Antigen
Peptide Fragments
Peptides
calcitonin gene-related peptide (8-37)
Adrenomedullin
9-(tetrahydro-2-furyl)-adenine
N-Formylmethionine Leucyl-Phenylalanine
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Adenine
Calcitonin Gene-Related Peptide