Cocaine enhances brain endothelial adhesion molecules and leukocyte migration

Leukocyte infiltration of cerebral vessels in cocaine-associated vasculopat hy suggests that cocaine may enhance leukocyte migration. We have investiga ted cocaine's effects on leukocyte adhesion in human brain microvascular en dothelial cell (BMVEC) cultures and monocyte migration in an in vitro blood -brain barrier (BBB) model constructed with BMVEC and astrocytes. Cocaine ( 10(-5) to 10(-9) M) enhanced adhesion of monocytes and neutrophils to BMVEC . In the BBB model, cocaine (10(-4) to 10(-8) M) enhanced monocyte transmig ration. Cocaine increased expression of endothelial adhesion molecules, int ercellular adhesion molecule-1 (ICAI-1, CD54), vascular cell adhesion molec ule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-l (ELAM-1) on B MVEC. The peak effect on ICAM-1 expression was between 6 and 18 h after tre atment. ICAM-1 was increased by cocaine in BMVEC, but not in human umbilica l vein endothelial cells, and the enhancement was greater in a coculture of BMVEC with monocytes. ICAM-1 expression was enhanced by a transcriptional mechanism. Polymyxin B inhibited up-regulation of adhesion molecules by LPS but not by cocaine. In LPS-activated BMVEC/monocyte coculture, cocaine inc reased secretion of-tumor necrosis factor-alpha and interIeukin-6. Taken to gether, these findings indicate that cocaine enhances leukocyte migration a cross the cerebral vessel wall, in particular under inflammatory conditions , but the effects are variable in different individuals. Cocaine's effects are exerted through a cascade of augmented expression of inflammatory cytok ines and endothelial adhesion molecules. These could underlie the cerebrova scular complications of cocaine abuse, (C) 1999 Academic Press.