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© 2002 American Heart Association, Inc.

Basic Science Reports

Influenza Infection Promotes Macrophage Traffic Into Arteries of Mice That Is Prevented by D-4F, an Apolipoprotein A-I Mimetic Peptide

From the Departments of Medicine (B.J.V.L., A.C.W., S.H., M.N., A.M.F.), Pathology and Laboratory Medicine (M.C.F.), and Microbiology, Immunology, and Molecular Genetics (D.P.N., L.A.), University of California at Los Angeles, and the Departments of Medicine, Biochemistry, and Molecular Genetics and the Atherosclerosis Research Unit (G.M.A., D.W.G.), University of Alabama, Birmingham.

Correspondence to Brian J. Van Lenten, PhD, Room 47-123 CHS, Division of Cardiology, Department of Medicine, UCLA School of Medicine, 10833 Le Conte Ave, Los Angeles, CA 90095-1679. E-mail bvanlent{at}mednet.ucla.edu

Background— We reported that HDL loses its antiinflammatory properties during acute influenza A infection in mice, and we hypothesized that these changes might be associated with increased trafficking of macrophages into the artery wall. The present study tested this hypothesis.

Methods and Results— D-4F, an apolipoprotein A-I mimetic peptide, or vehicle in which it was dissolved (PBS) was administered daily to LDL receptor–null mice after a Western diet and after influenza infection. D-4F treatment increased plasma HDL cholesterol and paraoxonase activity compared with PBS and inhibited increases in LDL cholesterol and peak levels of interleukin-6 after infection. Lung viral titers were reduced by 50% in mice receiving D-4F. Injection of female mice with male macrophages, which were detected with real-time polymerase chain reaction to measure the male Sry gene, revealed a marked increase in macrophage traffic into the aortic arch and innominate arteries after infection that was prevented by administration of D-4F.

Conclusions— We conclude that loss of antiinflammatory properties of HDL after influenza infection in mice is associated with increased arterial macrophage traffic that can be prevented by administration of D-4F.

Key Words: atherosclerosis • infection • lipoproteins • interleukins