RICKETTSIA-CONORII INFECTION ENHANCES VASCULAR CELL-ADHESION MOLECULE-1-DEPENDENT AND INTERCELLULAR-ADHESION MOLECULE-1-DEPENDENT MONONUCLEAR CELL ADHERENCE TO ENDOTHELIAL-CELLS

Leukocyte adherence to the endothelium is an essential component of th e inflammatory response during rickettsial infection. In vitro, Ricket tsia conorii infection of endothelial cells enhances the expression of adhesive molecules E-selectin, intercellular adhesion molecule-1 (ICA M-1), and vascular cell adhesion molecule-1 (VCAM-1) in a time- and do se-dependent manner. Rickettsial lipopolysaccharide doer; not seem to be involved, because polymyxin B does not reduce their expression. The intracellular presence of the organism and de novo host protein synth esis are required for expression of cell adhesive molecules, since ric kettsial inactivation by formol and pretreatment of cells with cyclohe ximide inhibits an increase in expression. The contribution of interle ukin-1 alpha (IL-1 alpha) to this endothelial adhesive phenotype was s hown by inhibitory experiments 8 and 24 h after infection with IL-1 re ceptor antagonist and IL-1 alpha blocking antibodies, Enhanced adheren ce of mononuclear cells to infected endothelial cells involved VCAM-1- and ICAM-1-dependent mechanisms at the late phase of the inflammatory response. This endothelial adhesive phenotype may constitute a key pa thophysiologic mechanism in R. conorii-induced vascular injury.