TY - JOUR
T1 - Regulated complement deposition on the surface of human endothelial cells
T2 - Effect of tobacco smoke and shear stress
AU - Yin, Wei
AU - Ghebrehiwet, Berhane
AU - Weksler, Babette
AU - Peerschke, Ellinor I.B.
N1 - Funding Information:
This work was supported in part by grants HL67211 (EIP) and AI060866 (BG) from the National Institutes of Health, and an American Heart Association Heritage Affiliate post doctoral award # 0625900T (WY).
PY - 2008
Y1 - 2008
N2 - Cigarette smoke and hemodynamic stress both contribute to vascular inflammation and associated atherosclerosis. We recently demonstrated direct activation of complement components C4 and C3 on human endothelial cells (EC). The present study was designed to explore complement activation on bone marrow microvascular endothelial cells (BMEC) and human umbilical vein endothelial cells (HUVEC) in response to endothelial cell injury by tobacco smoke extract, shear stress, or other known inflammatory and atherogenic mediators, lipopolysaccharide (LPS) and INF-γ. Following treatment, confluent EC monolayers were exposed to plasma (60 min, 37 °C), and cell surface deposition of stable complement derivatives C4d, iC3b and SC5b-9 was measured in situ using an ELISA approach. Consistent with previous results, moderate levels of C4d, iC3b and SC5b-9 deposition were observed on native EC monolayers exposed to human plasma. Tobacco smoke and shear stress enhanced EC C4d deposition. In contrast, LPS and INF-γ failed to affect EC mediated complement activation, despite evidence of EC activation illustrated by ICAM-1 expression. The combination of tobacco smoke and shear stress nearly doubled EC C4d expression. No increases in iC3b or SC5b-9 were noted, suggesting inhibition of classical and alternative pathway C3 convertase assembly or activity. Indeed, concomitantly increased surface expression of complement regulatory proteins CD35 (CR1) and CD55 was observed following EC exposure to tobacco smoke and shear stress. These results suggest that a balance between complement activation and regulation exists at the EC surface, and may impact vascular injury leading to thrombosis, arteriosclerosis, and atherogenesis.
AB - Cigarette smoke and hemodynamic stress both contribute to vascular inflammation and associated atherosclerosis. We recently demonstrated direct activation of complement components C4 and C3 on human endothelial cells (EC). The present study was designed to explore complement activation on bone marrow microvascular endothelial cells (BMEC) and human umbilical vein endothelial cells (HUVEC) in response to endothelial cell injury by tobacco smoke extract, shear stress, or other known inflammatory and atherogenic mediators, lipopolysaccharide (LPS) and INF-γ. Following treatment, confluent EC monolayers were exposed to plasma (60 min, 37 °C), and cell surface deposition of stable complement derivatives C4d, iC3b and SC5b-9 was measured in situ using an ELISA approach. Consistent with previous results, moderate levels of C4d, iC3b and SC5b-9 deposition were observed on native EC monolayers exposed to human plasma. Tobacco smoke and shear stress enhanced EC C4d deposition. In contrast, LPS and INF-γ failed to affect EC mediated complement activation, despite evidence of EC activation illustrated by ICAM-1 expression. The combination of tobacco smoke and shear stress nearly doubled EC C4d expression. No increases in iC3b or SC5b-9 were noted, suggesting inhibition of classical and alternative pathway C3 convertase assembly or activity. Indeed, concomitantly increased surface expression of complement regulatory proteins CD35 (CR1) and CD55 was observed following EC exposure to tobacco smoke and shear stress. These results suggest that a balance between complement activation and regulation exists at the EC surface, and may impact vascular injury leading to thrombosis, arteriosclerosis, and atherogenesis.
KW - Cigarette smoke
KW - Complement activation
KW - Endothelial cells
KW - Shear stress
UR - http://www.scopus.com/inward/record.url?scp=44549083235&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2007.11.005
DO - 10.1016/j.thromres.2007.11.005
M3 - Article
C2 - 18166221
AN - SCOPUS:44549083235
SN - 0049-3848
VL - 122
SP - 221
EP - 228
JO - Thrombosis Research
JF - Thrombosis Research
IS - 2
ER -