TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium

• Published in: PloS one Vol. 9; no. 8; p. e104588
• Main Authors: Lee, Seung Jin, Choi, Eun Kyoung, Seo, Kyo Won, Bae, Jin Ung, Park, So Youn, Kim, Chi Dae
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.08.2014; Public Library of Science (PLoS)
• Subjects: Adhesion; Animals; Aorta; Aorta - metabolism; Arachidonate 5-lipoxygenase; Arachidonate 5-Lipoxygenase - genetics; Arachidonate 5-Lipoxygenase - metabolism; Arteriosclerosis; Atherosclerosis; Attenuation; Biology and Life Sciences; Cell Adhesion; Cell adhesion molecules; Cell Line; Endothelial cells; Endothelium; Endothelium, Vascular - metabolism; Foam; Foams; Gene expression; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Immune system; In vivo methods and tests; Inflammation; Laboratory animals; Lipid A; Lipids; Lipoxygenase; Mac1 protein; Macrophage-1 Antigen - genetics; Macrophage-1 Antigen - metabolism; Medicine; Mice; Mice, Knockout; Monocytes; Monocytes - metabolism; mRNA; Neutrophils; Pathogenesis; Pharmacology; Proteins; Tissue engineering; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; United States > US; South Korea; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104588

Toll-like receptor 4 (TLR4) is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4-induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA), a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody, suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO) inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells induced by KLA were markedly attenuated. Moreover, KLA increased the expression of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these processes. In in vivo studies, KLA increased monocyte adhesion to aortic endothelium of wild-type (WT) mice, which was attenuated in WT mice treated with anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis.