Induction of mucosal tolerance to E-selectin targets immunomodulation to activating vessel segments and prevents ischemic and hemorrhagic stroke.

Abstract

Inflammatory and immune reactions at blood vessel segments that lead to local release of proinflammatory cytokines and local activation of luminal endothelium can initiate stroke (Hallenbeck et al. 1988; Libby et al. 1995). These multipotent autocrine or paracrine mediators can regulate expression of leukocyte adhesion molecules, production of other cytokines, growth factors, and chemokines, and production of matrix metalloproteinases in atherosclerosis. Local endothelium integrates extracellular signals and cellular responses in different regions of the vascular tree (Rosenberg and Aird 1999). Scattered perivascular ring patterns of immunoreactive tumor necrosis factor-alpha (TNF-α), heme oxygenase-1 (HO-1), and manganese superoxide dismutase (MnSOD) within the brain parenchyma of normal rats reflect cyclic activation and inactivation of brain vessel segments (Ruetzler et al. 2001). These cycles appear to be more frequent and intense in stroke-prone animals.