Connexin43 modulates neutrophil recruitment to the lung.

摘要: Transmigration of neutrophils through the microvascular endothelium is a cardinal event acute inflammation. It has been suggested that gap junctions made connexin43 (Cx43) may serve as conducting pathway to spread inflammatory signals within lung capillary network. To determine whether Cx43 contributes neutrophil transmigration in vivo, number transmigrated was monitored lungs mouse models subjected inflammation by intratracheal instillations Pseudomonas aeruginosa lipopolysaccharide (LPS). detected inflamed independently recruitment, whereas up-regulation not mice genetically protected from Mice heterozygous for gene (gja1) showed 56% (P < 0.01) reduction airway count. In contrast, increased 0.05) recruitment response LPS observed model expressing mutant with enhanced channel conductivity. vitro adhesion assays reduced conductivity channels (43)Gap26, blocking peptide, decreased endothelial cells. Finally, we found instillation (43)Gap26 65% 0.05). These results indicate mediators up-regulate alveolar promote airspace. therefore represent pharmacological target diseases characterized excessive airways.