Short-term sPECAM-Fc treatment ameliorates EAE while chronic use hastens onset of symptoms

Abstract

The homotypic cell adhesion molecule PECAM-1 is a major participant in the migration of leukocytes across endothelium. We examined the ability of a chimeric soluble sPECAM-1 fused to human IgGFc to impair leukocyte entry through the blood-brain barrier and reduce CNS autoimmunity. sPECAM-Fc impaired migration of lymphocytes across brain endothelial monolayers and diminished the severity of EAE, an experimental model of MS, when administered at the onset of symptoms. However, in mice transgenic for sPECAM-Fc, the chronically elevated levels of sPECAM-Fc hastened onset of EAE disease without significantly changing clinical score severity. Our data suggests that short-term treatment of diseases like MS with sPECAM-Fc has therapeutic potential.

An immunologist's guide to CD31 function in T-cells

“…The effects of blocking CD31 with antibodies are consistent with an adhesive function of this molecule as antibodies to CD31 have been shown to reduce leukocyte infiltration and disease severity dramatically in in vivo models of T-cell-mediated inflammation, including collagen-induced arthritis (CIA) (Ishikaw et al, 2002); (Decking et al, 2001) and experimental autoimmune encephalitis (Qing et al, 2001); (Bogen et al, 1994;Liao et al, 1997;Reinke et al, 2007;Vaporciyan et al, 1993).…”

“…In support of this interpretation, transgenic mice that chronically express high levels of circulating recombinant CD31 molecules (sPECAM-Fc) develop an earlier onset of EAE (Reinke et al, 2007). It is tempting to speculate that an overly high concentration of circulating CD31 ligand might have prevented CD31 signaling in T-cells by interfering with CD31 clustering, an effect known to occur in the presence of over-saturating concentrations of T-cell-stimulating antibodies (Roosnek et al, 1987).…”

Phytosterols ameliorate clinical manifestations and inflammation in experimental autoimmune encephalomyelitis

“…In order for macrophages to migrate to the CNS and induce damage, they must follow a chemotactic gradient stemming from the source of activity [36]. In EAE, it has been shown that tissues up-regulate the expression of multiple chemokines, thereby inducing cellular recruitment [15,30,37]. Moreover, studies conducted on EAE pathogenesis implicate a few specific chemokines in the induction of EAE [12].…”

Qigesan inhibits migration and invasion of esophageal cancer cells via inducing connexin expression and enhancing gap junction function

“…Tumor cell invasiveness was measured with a Transwell system (BD Biosciences, San Jose, CA, USA) [22]. The cells were treated with different concentrations of QGS (0, 50, or 100 μg/mL) for 24 h. The …”