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.

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.
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.
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.
AuthorsGuangyu An, Huan Wang, Rong Tang, Tadayuki Yago, J Michael McDaniel, Samuel McGee, Yuqing Huo, Lijun Xia
JournalCirculation (Circulation) Vol. 117 Issue 25 Pg. 3227-37 (Jun 24 2008) ISSN: 1524-4539 [Electronic] United States
PMID18519846 (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
  • 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

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