Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 227, Issue 12, Pages 3857-3875Publisher
WILEY
DOI: 10.1002/jcp.24100
Keywords
-
Categories
Funding
- Baylor College of Medicine New Investigator Start-up Program
- Guillain-Barre Syndrome/Chronic Inflammatory Demyelinating Polyradiculoneuropathy Foundation
- NIH [NS073702, NS075212, NS078226]
Ask authors/readers for more resources
The mechanisms of hematogenous leukocyte trafficking at the human bloodnerve barrier (BNB) are largely unknown. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the pathogenesis of GuillainBarre syndrome (GBS). We developed a cytokine-activated human in vitro BNB model using primary endoneurial endothelial cells. Endothelial treatment with 10?U/ml tissue necrosis factor-a and 20?U/ml interferon-? resulted in de novo expression of pro-inflammatory chemokines CCL2, CXCL9, CXCL11, and CCL20, with increased expression of CXCL23, CXCL8, and CXCL10 relative to basal levels. Cytokine treatment induced/enhanced ICAM-1, E- and P-selectin, vascular cell adhesion molecule-1 and the alternatively spliced pro-adhesive fibronectin variant, fibronectin connecting segment-1 expression in a time-dependent manner, without alterations in junctional adhesion molecule-A expression. Lymphocytes and monocytes from untreated GBS patients express ICAM-1 counterligands, aM- and aL-integrin, with differential regulation of aM-integrin expression compared to healthy controls. Under flow conditions that mimic capillary hemodynamics in vivo, there was a >3-fold increase in total GBS patient and healthy control mononuclear leukocyte adhesion/migration at the BNB following cytokine treatment relative to the untreated state. Function neutralizing monoclonal antibodies against human aM-integrin (CD11b) and ICAM-1 reduced untreated GBS patient mononuclear leukocyte trafficking at the BNB by 59% and 64.2%, respectively. Monoclonal antibodies against aL-integrin (CD11a) and human intravenous immunoglobulin reduced total leukocyte adhesion/migration by 22.8% and 17.6%, respectively. This study demonstrates differential regulation of aM-integrin on circulating mononuclear cells in GBS, as well as an important role for aM-integrinICAM-1 interactions in pathogenic GBS patient leukocyte trafficking at the human BNB in vitro. J. Cell. Physiol. 227: 38573875, 2012. (c) 2012 Wiley Periodicals, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available