Extravasation of polymorphonuclear leukocytes from the cerebral microvasculature. Inflammatory response induced by...

Postcapillary venules represent the segment of the microvasculature most vulnerable to inflammatory processes. While there is a considerable body of data on the peripheral vasculature, little is known about the primary events occurring during inflammatory reactions in cerebral blood vessels. We introduce here a model by which the migration of polymorphonuclear leukocytes through the CNS endothelial barrier can be studied. Alpha-bungarotoxin is used as a chemotactic agent and is shown, for the first time, to act by activating the complement cascade. Leukocytes migrate through the endothelium transcellularly. Two modes of migration are described: a direct mode whereby the cells use temporary pores in the vessel wall as portals, and an indirect mode whereby the leukocytes leave the vascular compartment after being enveloped by and incorporated into endothelial cells. The functional implications of these findings lead us to conclude that the direct mode of migration is a causal agent in the massive breakdown of the blood-brain barrier under acute inflammatory conditions.