Differential Responses to Lipopolysaccharide between Human and Baboon Arterial Endothelial Cells

Abstract

Since inflammation plays a critical role in atherosclerotic initiation, we want to know if endothelial cells from arterial vessels respond differently to proinflammatory stimuli among primates. Using cultured human arterial endothelial cells (HAECs) and baboon arterial endothelial cells (BAECs), we compared their responses to tumor necrosis factor-a (TNF-a) and LPS by measuring expression of cellular adhesion molecules and release of cytokines. We found that both HAECs and BAECs responded similarly to 10.0 ng/mL of TNF-a. However, HAECs showed significantly higher degree of response to LPS than BAECs. Treatment of 1.0 ug/mL of LPS led to a 3.7-fold increase in E-selectin expression and a 2.5-fold increase in ICAM-1 expression in HAECs, but there was no change in the expressions of E-selectin and ICAM in BAECs under the same conditions. LPS increased IL-8 release approximately 20.5-fold in HAECs, but it was only 2.9-fold in BAECs. LPS resulted in 7.8-fold and 4.9-fold MCP-1 increases in HAECs and BAECs, respectively. These expression differences were also confirmed at the level of mRNA expression using gene arrays. By determining their transcription factor activation levels, we found differential activation of p50 and p65 in HAECs and BAECs. Some components related to LPS-mediated signal pathway were also differentially expressed, indicating that BAECs have instinct hyporesponsive nature to LPS. Our current data suggest that arterial endothelial responses to proinflammatory stimuli were different between humans and baboons in response to different stimuli.