Influenza infection promotes macrophage traffic into arteries of mice that is prevented by D-4F, an apolipoprotein A-I mimetic peptide.
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.


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.
Van Lenten
Brian J
BJ
Department of Medicine, UCLA School of Medicine, University of California at Los Angeles, 90095-1679, USA. bvanlent@mednet.ucla.edu
Wagner
Alan C
AC
Anantharamaiah
G M
GM
Garber
David W
DW
Fishbein
Michael C
MC
Adhikary
Lopa
L
Nayak
Debi P
DP
Hama
Susan
S
Navab
Mohamad
M
Fogelman
Alan M
AM
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D016632:Apolipoprotein A-I / Q000031:analogs & derivatives* / Q000494:pharmacology*; D043303:Aryldialkylphosphatase; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D016122:Brachiocephalic Trunk / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D004036:Diet, Atherogenic; D004950:Esterases / Q000378:metabolism; D005260:Female; D024282:Genes, sry / Q000235:genetics; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood / Q000502:physiology; D008077:Lipoproteins, LDL / Q000097:blood; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010455:Peptides / Q000494:pharmacology*; D011014:Pneumonia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D016632:Apolipoprotein A-I; C465468:D-4F peptide; D015850:Interleukin-6; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010455:Peptides; D011973:Receptors, LDL; D004950:Esterases; D043303:Aryldialkylphosphatase