title: Crawling phagocytes recruited in the brain vasculature after pertussis toxin exposure through IL6, ICAM1 and ITGαM.
abstract: The cerebral vasculature is constantly patrolled by rod-shaped leukocytes crawling on the luminal endothelial surface. These cells are recruited in greater numbers after exposure to bacterial lipopolysaccharide (LPS) by a mechanism involving tumor necrosis factor (TNF), interleukin-1β (IL1β) and angiopoietin-2 (Angpt2). Here, we report that the population of crawling leukocytes, consisting mainly of granulocytes, is also increased in the brains of mice suffering from experimental autoimmune encephalomyelitis (EAE) or injected with pertussis toxin (PTX), which is commonly used to induce EAE. However, this recruitment occurs through an alternative mechanism, independent of Angpt2. In a series of experiments using DNA microarrays, knockout mice and neutralizing antibodies, we found that PTX acts indirectly on the endothelium in part through IL6, which is essential for the post-transcriptional upregulation of intercellular adhesion molecule 1 (ICAM1) in response to PTX but not to LPS. We also found that phagocytes adhere to brain capillaries through the interaction of integrin αM (ITGαM) with ICAM1 and an unidentified ligand. In conclusion, this study supports the concept that PTX promotes EAE, at least in part, by inducing vascular changes necessary for the recruitment of patrolling leukocytes.
authors.affiliation: Department of Endocrinology and Genomics, Laval University Hospital Research Center, Quebec City, Quebec, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Richard
authors.forename: Monica
authors.initials: M
authors.lastname: Roy
authors.forename: Julie
authors.initials: J
authors.lastname: Audoy-Rémus
authors.forename: Pierrot
authors.initials: P
authors.lastname: Tremblay
authors.forename: Luc
authors.initials: L
authors.lastname: Vallières
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006098:Granulocytes / Q000276:immunology* / Q000378:metabolism; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D037342:Pertussis Toxin / Q000494:pharmacology*; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: D000276:Adjuvants, Immunologic; D039481:CD11b Antigen; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1; D037342:Pertussis Toxin