INFECTION OF HUMAN VASCULAR ENDOTHELIAL-CELLS WITH STAPHYLOCOCCUS-AUREUS INDUCES HYPERADHESIVENESS FOR HUMAN MONOCYTES AND GRANULOCYTES

The consequences of internalization of Staphylococcus aureus by HUVEC with respect to their adhesiveness for human monocytes and granulocyte s were investigated. viable and UV-killed, but not heat-killed, S. aur eus were internalized by HUVEC, which required participation of the en dothelial cytoskeleton, S. aureus-infected HUVEC displayed increased s urface expression of CD106 (VCAM-1), CD54 (ICAM-1), and MHC I molecule s. Expression of CD62P (P-selectin), CD62E (E-selectin), CD31 (PECAM-1 ), and CD102 (ICAM-2) was not affected. Concomitantly, these HUVEC exp ressed a time- and inoculum size-dependent hyperadhesiveness for monoc ytes and granulocytes. Monocyte adhesion reached maximal levels (simil ar to 60% adhesion) 23 h after the initial 1 h period of infection of HUVEC with about 50 bacteria per single HUVEC. To induce maximal (simi lar to 20%) adhesion of granulocytes, five times higher concentrations of HUVEC-infecting bacteria were required, Using the appropriate mAb, granulocyte adhesion to S. aureus-infected HUVEC was shown to be enti rely mediated by the beta(2) (CD11/CD18) integrins. Monocyte adhesion to these HUVEC was largely (similar to 70%) dependent on both CD11a/CD 18 (LFA-1) and CD49d/CD29 (VLA-4). This demonstrates that infection of HUVEC with S. aureus potentiates CD11/CD18-mediated granulocyte adhes ion and shifts the mechanism of monocyte adhesion from being completel y CD11/CD18 dependent to one that also utilizes the VLA-4/ VCAM-1 depe ndent pathway. Together, these findings indicate that in response to i nternalization of S. aureus, vascular endothelial cells may initiate r ecruitment of monocytes and granulocytes, which may be an important in itial event in the pathogenesis of endovascular diseases.