GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

TableEdit

Jump to: navigation, search

PMID:11549596

You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor

Citation

Collard, CD, Montalto, MC, Reenstra, WR, Buras, JA and Stahl, GL (2001) Endothelial oxidative stress activates the lectin complement pathway: role of cytokeratin 1. Am. J. Pathol. 159:1045-54

Abstract

Oxidative stress increases endothelial mannose-binding lectin (MBL) binding and activates the lectin complement pathway (LCP). However, the molecular mechanism of MBL binding to the endothelium after oxidative stress is unknown. Intermediate filaments have been previously reported to activate the classical complement pathway in an antibody-independent manner. We investigated whether oxidative stress increases human umbilical vein endothelial cell (HUVEC) cytokeratin 1 (CK1) expression and activates the LCP via MBL binding to CK1. Reoxygenation (3 hours, 21% O(2)) of hypoxic HUVECs (24 hours, 1% O(2)) significantly increased CK1 mRNA (in situ hybridization) and membrane protein expression [enzyme-linked immunosorbent assay (ELISA)/confocal microscopy]. Incubating human serum (HS) with N-acetyl-D-glucosamine or anti-human MBL monoclonal antibody attenuated MBL and C3 deposition on purified CK1 (ELISA). CK1 and MBL were co-immunoprecipitated from hypoxic HUVECs reoxygenated in HS. Treatment with anti-human cytokeratin Fab fragments attenuated endothelial MBL and C3 deposition after oxidative stress (ELISA/confocal microscopy). We conclude that: 1) endothelial oxidative stress increases CK1 expression, MBL binding, and C3 deposition; 2) inhibition of MBL attenuates purified CK1-induced complement activation; and 3) anti-human cytokeratin Fab fragments attenuate endothelial MBL and C3 deposition after oxidative stress. These results suggest that MBL binding to endothelial cytokeratins may mediate LCP activation after oxidative stress.

Links

PubMed PMC1850443 Online version:10.1016/S0002-9440(10)61779-8

Keywords

Antibodies/pharmacology; Blotting, Western; Carrier Proteins/antagonists & inhibitors; Carrier Proteins/metabolism; Cells, Cultured; Collectins; Complement C3/antagonists & inhibitors; Complement C3/metabolism; Complement System Proteins/metabolism; Endothelium, Vascular/metabolism; Humans; Keratins/genetics; Keratins/immunology; Keratins/metabolism; Keratins/physiology; Lectins/metabolism; Oxidative Stress/drug effects; Precipitin Tests; RNA, Messenger/metabolism

public



Cancel