Objective - Core2 1-6-N-glucosaminyltransferase-I (C2G1cNAcT-I) modification of adhesion molecules is required for optimal binding to target ligands. The objective of this study was to determine the role of C2G1cNAcT-I in the recruitment of Ly-6Chi monocytes to atherosclerotic lesions and in lesion formation in mice. Methods and Results - In a whole-blood binding assay, Ly-6Chi monocytes and certain lymphocytes and natural killer cells from wild-type mice bound to P- and E-selectin. C2G1cNAcT-I deficiency abrogated leukocyte binding to P- and E-selectin in this assay as well as in an in vitro flow chamber assay. Moreover, C2G1cNAcT-I deficiency decreased Ly-6Chi monocyte interactions with atherosclerotic arteries under physiological flow conditions and also inhibited monocyte recruitment to the peritoneal cavity in mice challenged with thioglycollate. In apolipoprotein E-deficient (apoE-/-) mice, lack of C2G1cNAcT-I resulted in fewer and smaller atherosclerotic lesions in mouse aortas. Atherosclerosis was also suppressed in C2G1cNAcT-I-/-/apoE-/- chimeric mice transplanted with C2G1cNAcT-I+/+ bone marrow cells. Conclusions - C2G1cNAcT-I in both leukocytes and blood vessel wall cells contributes to leukocyte recruitment to the arterial wall. C2G1cNAcT-I deficiency leads to the formation of small, macrophage-poor, and collagen-rich atherosclerotic lesions.
|Original language||English (US)|
|Number of pages||8|
|Journal||Arteriosclerosis, thrombosis, and vascular biology|
|State||Published - Feb 1 2009|
- Adhesion molecule
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine