title: Infection of human vascular endothelial cells with Staphylococcus aureus induces hyperadhesiveness for human monocytes and granulocytes.
abstract: The consequences of internalization of Staphylococcus aureus by HUVEC with respect to their adhesiveness for human monocytes and granulocytes were investigated. Viable and UV-killed, but not heat-killed, S. aureus were internalized by HUVEC, which required participation of the endothelial cytoskeleton. S. aureus-infected HUVEC displayed increased surface expression of CD106 (VCAM-1), CD54 (ICAM-1), and MHC I molecules. Expression of CD62P (P-selectin), CD62E (E-selectin), CD31 (PECAM-1), and CD102 (ICAM-2) was not affected. Concomitantly, these HUVEC expressed a time- and inoculum size-dependent hyperadhesiveness for monocytes and granulocytes. Monocyte adhesion reached maximal levels (approximately 60% adhesion) 23 h after the initial 1 h period of infection of HUVEC with about 50 bacteria per single HUVEC. To induce maximal (approximately 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 entirely mediated by the beta2 (CD11/CD18) integrins. Monocyte adhesion to these HUVEC was largely (approximately 70%) dependent on both CD11a/CD18 (LFA-1) and CD49d/CD29 (VLA-4). This demonstrates that infection of HUVEC with S. aureus potentiates CD11/CD18-mediated granulocyte adhesion and shifts the mechanism of monocyte adhesion from being completely CD11/CD18 dependent to one that also utilizes the VLA-4/VCAM-1 dependent pathway. Together, these findings indicate that in response to internalization of S. aureus, vascular endothelial cells may initiate recruitment of monocytes and granulocytes, which may be an important initial event in the pathogenesis of endovascular diseases.
authors.affiliation: Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Beekhuizen
authors.forename: J S
authors.initials: JS
authors.lastname: van de Gevel
authors.forename: B
authors.initials: B
authors.lastname: Olsson
authors.forename: I J
authors.initials: IJ
authors.lastname: van Benten
authors.forename: R
authors.initials: R
authors.lastname: van Furth
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000382:microbiology*; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D014471:Umbilical Veins / Q000166:cytology / Q000382:microbiology
chemical_list: D015815:Cell Adhesion Molecules