Neutrophil transendothelial migration and alteration in vascular permeability: focus on neutrophil-derived azurocidin.

Infiltration and accumulation of polymorphonuclear leukocytes within the tissues is a hallmark of the acute inflammatory response. A prominent feature of acute inflammation is enhanced vascular permeability resulting in edema formation. Such changes in vascular permeability have been known to be dependent upon polymorphonuclear leukocyte interactions with the vascular endothelium. Careful investigation has shown clearly that permeability changes can occur without polymorphonuclear leukocyte transendothelial migration, and that polymorphonuclear leukocyte migration can occur without permeability alteration. The underlying mechanisms of polymorphonuclear leukocyte-stimulated changes in endothelial barrier function have remained elusive. Endothelial activation and polymorphonuclear leukocyte adhesion to the endothelium are both required for polymorphonuclear leukocyte-induced changes in vascular permeability. Polymorphonuclear leukocyte-derived azurocidin plays a major role in this polymorphonuclear leukocyte-evoked alteration in endothelial permeability. Azurocidin is released after activation of polymorphonuclear leukocytes, such as after ligation of the major adhesive integrin CD11b/CD18. Understanding how polymorphonuclear leukocytes alter vascular permeability may provide targets for new drugs for appropriate therapeutic intervention in acute and chronic inflammatory diseases. This review focuses on the role of polymorphonuclear leukocyte-derived azurocidin in alteration of vascular permeability.