Rickettsia conorii infection enhances vascular cell adhesion molecule-1- and intercellular adhesion molecule-1-dependent mononuclear cell adherence to endothelial cells.
Leukocyte adherence to the endothelium is an essential component of the inflammatory response during rickettsial infection. In vitro, Rickettsia conorii infection of endothelial cells enhances the expression of adhesive molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in a time- and dose-dependent manner. Rickettsial lipopolysaccharide does not seem to be involved, because polymyxin B does not reduce their expression. The intracellular presence of the organism and de novo host protein synthesis are required for expression of cell adhesive molecules, since rickettsial inactivation by formol and pretreatment of cells with cycloheximide inhibits an increase in expression. The contribution of interleukin-1alpha (IL-1alpha) to this endothelial adhesive phenotype was shown by inhibitory experiments 8 and 24 h after infection with IL-1 receptor antagonist and IL-1alpha blocking antibodies. Enhanced adherence 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 pathophysiologic mechanism in R. conorii-induced vascular injury.
Dignat-George
F
F
Laboratoire d'Hématologie et d'Immuno-Hématologie, Unité de Formationet de Recherche (UFR) de Pharmacie-27, Marseille, France.
Teysseire
N
N
Mutin
M
M
Bardin
N
N
Lesaule
G
G
Raoult
D
D
Sampol
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003513:Cycloheximide / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000382:microbiology* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*; D053590:Interleukin 1 Receptor Antagonist Protein; D009000:Monocytes / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012281:Rickettsia / Q000502:physiology*; D012795:Sialoglycoproteins / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*; D014709:Vero Cells
D000911:Antibodies, Monoclonal; D019040:E-Selectin; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003513:Cycloheximide