Listeria monocytogenes infection and activation of human brain microvascular endothelial cells

Listeria monocytogenes invasion of human brain microvascular endothelial ce lls (BMEC) and its role as a stimulus for endothelial cell activation were studied. Binding and invasion of intact BMEC monolayers were independent of the L. monocytogenes inlAB invasion locus. Cytochalasin D abrogated invasi on of BMEC, whereas genistein effected only a 53% decrease in invasion, ind icating a requirement for rearrangement of actin microfilaments but less de pendence on tyrosine kinase activity. L, monocytogenes stimulated surface e xpression of E-selectin, ICAM-1, and to a lesser extent, VCAM-1, whereas L. monocytogenes prfA - and Delta hly mutants were severely compromised in th is respect. Other experiments showed that BMEC infection stimulated monocyt e and neutrophil adhesion and that CD18-mediated binding was the predominan t mechanism for neutrophil adhesion to infected BMEC under static condition s. These data suggest that invasion of BMEC is a mechanism for triggering i nflammation and leukocyte recruitment into the central nervous system durin g bacterial meningitis.