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Comparative analysis of vascular endothelial cell activation by TNF-α and LPS in humans and baboons

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Abstract

As an Old World nonhuman primate, baboons have been extensively used for research on dyslipidemia and atherogenesis. With increasing knowledge about the endothelium's role in the initiation and progression of atherosclerosis, the value of the baboon model can be increased by developing it for research on the role of dysfunctional endothelium in atherogenesis. Toward that goal, we have established and validated methods of isolating and culturing baboon femoral artery endothelial cells (BFAECs) and compared baboon endothelial cellular characteristics with those of humans. Our results indicated that baboon and human endothelial cells share similar growth and culture behaviors. As was the case for human endothelial cells, BFAECs responded to tumor necrosis factor (TNF)-α stimulation with increased expression of adhesion molecules (maximum increase for intracellular adhesion molecule (ICAM): 1.76±0.26-fold; vascular cell adhesion molecule (VCAM): 1.65±0.25-fold; E-selectin: 2.86±0.57-fold). However, BFAECs were hyporesponsive to lipopolysaccharide (LPS) (range, 0.25–20 μg/mL) in adhesion molecule expression, whereas 1 μg/mL LPS induced 2.14- to 3.71-fold increases in human endothelial cells. The differential responses to LPS were not related to TLR-2 and toll-like receptor (TLR)-4 expression on the cell surface. And baboon microvascular endothelial cells had similar features as BFAECs. We observed constitutive expression of interleukin (IL)-6, IL-8, granulocyte macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein (MCP)-1 in both human and baboon endothelial cells, and these cytokines were further induced by TNF-α and LPS. We also demonstrated that the responses to TNF-α or LPS varied among baboons maintained under the same dietary and environmental conditions, suggesting that response may be controlled by genetic factors.

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Authors and Affiliations

  1. Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio

    Qiang Shi, Jian Wang, Xing Li Wang & John L. VandeBerg

  2. Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio

    John L. VandeBerg

  3. Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX

    Jian Wang & Xing Li Wang

Authors
  1. Qiang Shi
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  2. Jian Wang
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  3. Xing Li Wang
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  4. John L. VandeBerg
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Correspondence to Xing Li Wang.

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Shi, Q., Wang, J., Wang, X.L. et al. Comparative analysis of vascular endothelial cell activation by TNF-α and LPS in humans and baboons. Cell Biochem Biophys 40, 289–303 (2004). https://doi.org/10.1385/CBB:40:3:289

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