Details

Autor(en) / Beteiligte

• Richard, Jean-François
• Roy, Monica
• Audoy-Rémus, Julie
• Tremblay, Pierrot
• Vallières, Luc

Titel

Crawling Phagocytes Recruited in the Brain Vasculature after Pertussis Toxin Exposure through IL6, ICAM1 and ITGαM

Ist Teil von

• Brain pathology (Zurich, Switzerland), 2011-11, Vol.21 (6), p.661-671

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Wiley Online Library

Beschreibungen/Notizen

• 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.