Modulation of PMN-Endothelial Cells Interactions by Cyclic Nucleotides

Yukio      Sato

Abstract

Polymorphonuclear leukocytes (PMN) interact with endothelial cells (EC) under normal and diseased conditions. Common mechanisms exist regulating PMN-EC interactions in the systemic and pulmonary circulations and adhesion molecules play significant roles in both circulations, however there are important differences. Alterations in PMN deformability appear to be important in the pulmonary circulation because of the unique geometric and hydrodynamic conditions that exist in the pulmonary microvasculature. PMN work as the hosts first line of defense against invading pathogens. Under certain circumstances, however, dysregulation of PMN-EC interactions may contribute to local or global tissue injury in diseases such as acute respiratory syndrome and multiple organ failure syndrome. Therefore, a thorough understanding of the regulation of PMN-EC interactions is important to understand the pathogenesis of this type of tissue injury, and modulation of PMN-EC interactions could be applicable to prevent or treat injury. cGMP and cAMP are cyclic nucleotides that work as second messengers and control numerous functions in PMN. This review covers the modulation of PMN-EC interactions with cGMP and cAMP. Recent studies have shown that both cGMP and cAMP have inhibitory effects on events such as rolling, adhesion, migration and deformability change of PMN that are essential to PMN-EC interactions. Therefore, it is expected that the modulation of cyclic nucleotides is applicable for the treatment not only of local inflammatory diseases such as asthma but also of global tissue injury such as acute respiratory distress syndrome.

Keywords: neutrophil, endothelium, adhesion molecules, cytoskeleton, f-actin, nitric oxide, phosphodiesterase, endothelin