P-selectin glycoprotein ligand-1 is highly expressed on Ly-6Chi monocytes and a major determinant for Ly-6Chi monocyte recruitment to sites of atherosclerosis in mice.

Abstract

BACKGROUND:

Ly-6C(hi) monocytes are key contributors to atherosclerosis in mice. However, the manner in which Ly-6C(hi) monocytes selectively accumulate in atherosclerotic lesions is largely unknown. Monocyte homing to sites of atherosclerosis is primarily initiated by rolling on P- and E-selectin expressed on endothelium. We hypothesize that P-selectin glycoprotein ligand-1 (PSGL-1), the common ligand of P- and E-selectin on leukocytes, contributes to the preferential homing of Ly-6C(hi) monocytes to atherosclerotic lesions.

METHODS AND RESULTS:

To test this hypothesis, we examined the expression and function of PSGL-1 on Ly-6C(hi) and Ly-6C(lo) monocytes from wild-type mice, ApoE(-/-) mice, and mice lacking both ApoE and PSGL-1 genes (ApoE(-/-)/PSGL-1(-/-)). We found that Ly-6C(hi) monocytes expressed a higher level of PSGL-1 and had enhanced binding to fluid-phase P- and E-selectin compared with Ly-6C(lo) monocytes. Under in vitro flow conditions, more Ly-6C(hi) monocytes rolled on P-, E-, and L-selectin at slower velocities than Ly-6C(lo) cells. In an ex vivo perfused carotid artery model, Ly-6C(hi) monocytes interacted preferentially with atherosclerotic endothelium compared with Ly-6C(lo) monocytes in a PSGL-1-dependent manner. In vivo, ApoE(-/-) mice lacking PSGL-1 had impaired Ly-6C(hi) monocyte recruitment to atherosclerotic lesions. Moreover, ApoE(-/-)/PSGL-1(-/-) mice exhibited significantly reduced monocyte infiltration in wire injury-induced neointima and in atherosclerotic lesions. ApoE(-/-)/PSGL-1(-/-) mice also developed smaller neointima and atherosclerotic plaques.

CONCLUSIONS:

These data indicate that PSGL-1 is a new marker for Ly-6C(hi) monocytes and a major determinant for Ly-6C(hi) cell recruitment to sites of atherosclerosis in mice.

• Authors: Guangyu An, Huan Wang, Rong Tang, Tadayuki Yago, J Michael McDaniel, Samuel McGee, Yuqing Huo, Lijun Xia
• Journal: Circulation (Circulation) Vol. 117 Issue 25 Pg. 3227-37 (Jun 24 2008) ISSN: 1524-4539 [Electronic] United States
• PMID: 18519846 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, Ly
• Apolipoproteins E
• E-Selectin
• Ly-6C antigen, mouse
• Membrane Glycoproteins
• P-Selectin
• P-selectin ligand protein
• RNA, Messenger

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Antigen-Antibody Reactions
• Antigens, Ly (biosynthesis)
• Apolipoproteins E (deficiency)
• Atherosclerosis (genetics, immunology)
• Binding Sites
• Carotid Artery Injuries (genetics, immunology)
• Cell Adhesion (immunology)
• Chemotaxis, Leukocyte (immunology)
• Disease Models, Animal
• E-Selectin (metabolism)
• Flow Cytometry
• Membrane Glycoproteins (biosynthesis, deficiency, genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Monocytes (immunology)
• P-Selectin (metabolism)
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction