Mouse monoclonal anti-human thrombomodulin antibodies bind to and activate endothelial cells through NF-kappaB activation in vitro

Arthritis and Rheumatism
Hiroyuki NaraTaku Yoshio

Abstract

To clarify whether mouse monoclonal antibodies (mAb) against human thrombomodulin (TM), which react with human TM present on the endothelial cell (EC) surface, have anti-endothelial cell antibody (AECA) activity and influence antiinflammatory properties of human TM expressed on the EC surface in vitro. Three preparations of mouse mAb against human TM that react with different sites of the human TM epidermal growth factor-like domain were tested for their ability to 1) bind to ECs, 2) modulate cytokine secretion from ECs, EC adhesion molecule expression, and neutrophil adhesion to ECs, and 3) stimulate nuclear translocation of NF-kappaB through the degradation of cytoplasmic IkappaB in ECs. Recombinant human interleukin-1beta (IL-1beta) was used as a positive control, and mouse IgG1 and mouse IgG2a were used as negative controls. The 3 preparations of mouse mAb against human TM that bind to unfixed EC monolayers enhanced IL-6 and IL-8 secretion from ECs, up-regulated expression of endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 on EC monolayers, and enhanced neutrophil adhesion to ECs to a degree similar to that observed with IL-1beta stimulation, but they did n...Continue Reading

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Citations

Aug 29, 2007·Journal of the American Society of Nephrology : JASN·Caroline O S Savage, Julie M Williams
Apr 23, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Fiona A MartinPhilip M Cummins
Jan 20, 2019·Nature Reviews. Rheumatology·Noa SchwartzChaim Putterman
Dec 5, 2006·Current Opinion in Rheumatology

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