Premium
Monocyte CD11c/CD18 expression is upregulated postprandially and mediates firm arrest on VCAM‐1
Author(s) -
Gower R Michael,
Wu Huaizhu,
Knowlton Anne A,
Ballantyne Christie M,
Simon Scott I
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.640.5
Subject(s) - monocyte , cd11c , cd18 , vcam 1 , endocrinology , medicine , immunology , chemistry , cell adhesion molecule , receptor , biology , integrin alpha m , icam 1 , phenotype , biochemistry , gene
Atherosclerosis is an inflammatory disease initiated by hyperlipidemia and monocyte recruitment. Low shear stress and cytokine activation increases VCAM‐1 expression, the principle endothelial receptor facilitating monocyte arrest. We reported that monocyte integrin CD11c/CD18 binds VCAM‐1 and cooperates with VLA‐4 to arrest monocytes on inflamed endothelium. In this study, we determined if CD11c expression on monocytes from 60 human donors increased in a hyperlipidemic state. Blood was drawn from fasting donors and again at 3.5hrs after a 45% fat meal. Resting and MCP‐1 stimulated levels of CD11c on monocytes were increased after the meal. Highest CD11c expression correlated with high blood levels of total cholesterol (>200mg/dL) and low HDL (<35mg/dL). To assess the role of CD11c in recruitment, monocytes were isolated from ApoE −/− /CD11c −/− mice and perfused through a microfluidic chamber derivatized with VCAM‐1 and E‐selectin. When CD11c was absent there was a 45% decrease in firm arrest compared to CD11c +/+ cells. Antibody blocking of VLA‐4 inhibited monocyte arrest to a similar extent for both genotypes. When firmly arrested monocytes were exposed to a 5‐fold increase in shear stress, 40% more CD11c +/+ cells remained firmly arrested. We conclude hyperlipidemia associated with a high fat meal can upregulate monocyte CD11c, and its binding to VCAM‐1 is a critical step in high avidity monocyte adhesion. Research supported by HL082689 to S.I.S. and T32 HL086350‐01A1 to R.M.G.