Monocyte chemoattractant protein-1 but not tumor necrosis factor-alpha is correlated with monocyte infiltration in mouse lipid lesions.
BACKGROUND
Apolipoprotein (apo)(a) transgenic mice and C57BL/6 mice fed a high fat diet develop similar-sized lipid lesions, but lesions in apo(a) mice are devoid of macrophages. We used this observation to identify which proinflammatory proteins might be involved in mediating monocyte recruitment during atherogenesis.


RESULTS
Macrophage-deficient apo(a) transgenic mouse lesions contained similar levels of several different proinflammatory proteins, both adhesion molecules (intercellular adhesion molecule-1 [ICAM-1] and vascular cell adhesion molecule-1 [VCAM-1]) and cytokines (tumor necrosis factor-alpha [TNF-alpha] and macrophage inflammatory protein-1alpha [MIP-1alpha]), similar to the macrophage-rich lesions of C57BL/6 mice.


CONCLUSIONS
From this we conclude that ICAM-1, VCAM-1, TNF-alpha, and MIP-1alpha may all be necessary for vascular monocyte recruitment in vivo, but they cannot be sufficient. Monocyte chemoattractant protein-1 (MCP-1) protein was undetectable in the vessel wall taken from apo(a) transgenic mice fed a high fat diet compared with high expression in mice with lipid lesions (C57BL/6 and apoE knockout mice). Therefore elevated expression of MCP-1 but not TNF-alpha, MIP-1alpha, ICAM-1, or VCAM-1 is correlated with vascular macrophage accumulation. To test the hypothesis that monocyte infiltration during atherogenesis is MCP-1 dependent, it will be necessary to develop specific pharmacological inhibitors of MCP-1 activity.
Reckless
J
J
Departments of Biochemistry and Medicine, University of Cambridge, UK. jr219@mole.bio.cam.ac.uk
Rubin
E M
EM
Verstuyft
J B
JB
Metcalfe
J C
JC
Grainger
D J
DJ
D000818:Animals; D001053:Apolipoproteins / Q000502:physiology; D053241:Apoprotein(a); D001161:Arteriosclerosis / Q000473:pathology*; D018932:Chemokine CCL2 / Q000032:analysis*; D004041:Dietary Fats / Q000633:toxicity*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D017270:Lipoprotein(a); D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D001053:Apolipoproteins; D018932:Chemokine CCL2; D004041:Dietary Fats; D017270:Lipoprotein(a); D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D053241:Apoprotein(a)