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P‐selectin mediates both arteriolar dysfunction and venular inflammation associated with cytomegalovirus and hypercholesterolemia
Author(s) -
Stokes Karen Y.,
Johnson Eunice
Publication year - 2007
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.21.6.a850
Subject(s) - inflammation , immunology , cell adhesion molecule , vasodilation , p selectin , cremaster muscle , cytomegalovirus , adhesion , endothelial dysfunction , medicine , microcirculation , chemistry , platelet , virus , herpesviridae , platelet activation , viral disease , organic chemistry
Cytomegalovirus (CMV), a β‐herpesvirus, has been implicated in the inflammation associated with several vascular diseases. CMV upregulates adhesion molecules and induces leukocyte adhesion in vitro. This study examines the role of P‐selectin in the microvascular inflammation that occurs in hypercholesterolemic mice infected with CMV. C57Bl/6 mice were mock‐inoculated or infected with murine CMV, and 5wk later placed on normal diet (ND) or high cholesterol diet (HC) for 4wk. Separate CMV‐HC groups received P‐selectin blocking Ab 18 h before observation. Acetylcholine‐induced arteriolar vasodilation and leukocyte adhesion in postcapillary venules were monitored in the cremaster muscle. CMV alone, but not HC alone, impaired arteriolar function. However, leukocyte adhesion was only elevated when CMV was combined with HC. Pre‐treatment of CMV‐HC mice with P‐selectin Ab reduced leukocyte adhesion to levels observed in mock‐ND mice. Blocking P‐selectin also conferred protection against arteriolar dysfunction in this group. These findings implicate P‐selectin in the leukocyte recruitment elicited by CMV infection combined with hypercholesterolemia, and suggest that P‐selectin contributes to arteriolar dysfunction through a pathway that is independent of leukocyte adhesion in these vessels. (Supported by AHA 0565285B).