title: LPS differentially regulates adhesion and transendothelial migration of human monocytes under static and flow conditions.
abstract: One of the key components of the innate immune response is the recognition of microbial products such as LPS by Toll-like receptors on monocytes and neutrophils. We show here that short-term stimulation of primary human monocytes with LPS led to an increase in adhesion of monocytes to endothelial cells and a dramatic decrease in transendothelial migration under static conditions. In contrast, under normal physiological flow, monocyte adhesion and migration across a human umbilical vein endothelial cell monolayer appeared to be unaffected by LPS treatment. LPS stimulation of monocytes activated beta(1) and beta(2) integrins, but did not increase their surface expression levels. During septic shock, reduction in blood flow as a result of vasodilation and vascular permeability leads to adhesion and accumulation of LPS-stimulated circulating monocytes onto the blood vessel walls. The different findings of monocyte migration under static and flow conditions in our study may offer one explanation for this phenomenon. The rapid engagement of LPS-activated monocytes preventing transendothelial migration could represent a novel mechanism of bacterial exclusion from the vasculature. This occurs during the early stages of sepsis, and in turn may modulate the severity of the pathophysiology.
authors.affiliation: Department of Pathology and Immunology, University Medical Centre, 1 Rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Bradfield
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Johnson-Léger
authors.forename: Claudia
authors.initials: C
authors.lastname: Zimmerli
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
mesh_terms: D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002464:Cell Migration Inhibition; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D014471:Umbilical Veins
chemical_list: D018821:CD18 Antigens; D008070:Lipopolysaccharides