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.
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.


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.
An
Guangyu
G
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Wang
Huan
H
Tang
Rong
R
Yago
Tadayuki
T
McDaniel
J Michael
JM
McGee
Samuel
S
Huo
Yuqing
Y
Xia
Lijun
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000950:Antigens, Ly / Q000096:biosynthesis*; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites; D020212:Carotid Artery Injuries / Q000235:genetics / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D005434:Flow Cytometry; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D019007:P-Selectin / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D001057:Apolipoproteins E; D019040:E-Selectin; C494192:Ly-6C antigen, mouse; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D012333:RNA, Messenger