Firm adhesion of neutrophils to cerebral vascular endothelium "in vivo": a role for cys-leukotrienes.

Interactions between neutrophils (PMNL) and endothelial cells (EC) are involved in pathological alterations of cerebral blood vessel functions, leading to circulatory disturbances such as stroke [1]. The adhesive process induces PMNL activation, coupled to local bioavailability of oxygen free radicals, proteases, cytokines and arachidonate metabolites of the 5- lipoxygenase pathway, such as leukotriene A4 and B4 (LTA4, LTB4). This contributes to alterations of vasomotor reactivity, occlusion of microvasculature and induction of vascular permeability. The ensuing PMNL emigration through the blood brain barrier represents a critical event in the initiation of cerebral inflammation. Therefore it is clear that the PMNL-EC interaction may be a target for therapeutic interventions. Significant reductions in volume of the lesions and improved physiological functions were found in rats subjected to transient MCA occlusion and treated with anti-ICAM antibody, as well as with selective PMNL depletion in a murine model of reperfused stroke.