Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE-/- mice.
Allograft inflammatory factor (AIF)-1, originally cloned from a rat heart allograft under chronic rejection, is induced in various inflammatory conditions including atherosclerosis. Using mouse AIF-1 transfected macrophages and AIF-1 transgenic (AIF-1 Tg) mice, we analyzed the influence of AIF-1 overexpression on macrophage phagocytosis and the development of atherosclerosis. The AIF-1 transfectants showed significantly increased phagocytosis of latex beads and E. coli BioParticles as well as incorporation of acetylated low-density lipoprotein (LDL) compared to those of vector controls. Concordant results were obtained with elicited peritoneal exudate cells from AIF-1 Tg mice. When AIF-1 Tg mice were crossbred with apolipoprotein E knockout mice (ApoE-/-), these AIF-1 Tg ApoE-/- mice developed significantly increased atherosclerotic lesions compared to ApoE-/- mice. These results suggest that enhanced AIF-1 expression leads to augmented incorporation of degenerated LDL by macrophages and promotes development of atherosclerotic vasculopathy.
Mishima
Tetsuya
T
Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Iwabuchi
Kazuya
K
Fujii
Satoshi
S
Tanaka
Shin-Ya
SY
Ogura
Hisako
H
Watano-Miyata
Keiko
K
Ishimori
Naoki
N
Andoh
Yasuhiro
Y
Nakai
Yukihito
Y
Iwabuchi
Chikako
C
Ato
Manabu
M
Kitabatake
Akira
A
Tsutsui
Hiroyuki
H
Onoé
Kazunori
K
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D018450:Disease Progression; D005122:Exudates and Transudates; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins; D008863:Microspheres; D010587:Phagocytosis; D014162:Transfection
C491049:Aif1 protein, mouse; D001057:Apolipoproteins E; D002135:Calcium-Binding Proteins; D008077:Lipoproteins, LDL; D008840:Microfilament Proteins; C032629:acetyl-LDL; D016650:Fluorescein-5-isothiocyanate