Polymorphonuclear leukocyte--endothelium interactions: a role for pro-inflammatory and anti-inflammatory molecules

The movement of polymorphonuclear leukocytes (PMNs) from the mainstream of blood to the extravascular space is a characteristic feature of the inflammatory response. This process requires that the PMN initially contacts the endothelium, then adheres firmly to the vessel wall, and finely migrates out of the microvasculature. Each of these events requires signals or pro-inflammatory molecules that direct the PMN to the potential site of inflammation. These molecules include histamine, which appears to be of importance in the initial recruitment of PMNs, leukotriene B4, which promotes PMN adhesion, and platelet-activating factor, which may contribute to both the adhesion process as well as the migration through the endothelial barrier. Although many other pro-inflammatory molecules have been identified, including the cytokines and complement, the three aforementioned molecules are used in this review as paradigms of the varying functions that pro-inflammatory molecules have in the inflammatory process. There is a growing body of evidence that in addition to the many pro-inflammatory agents found in the body there are a number of important anti-inflammatory molecules, including nitric oxide, prostacyclin, and adenosine. Each of these molecules possess important properties that serve to interrupt or protect against the ongoing inflammatory process. The anti-inflammatory potential of these endogenous molecules is discussed.