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Department of Molecular and Cellular Physiology, Health Sciences Center, Louisiana State University, Shreveport, Louisiana 71130-3932
Submitted 15 June 2003 ; accepted in final form 5 August 2003
We have previously shown that T lymphocytes and interferon-
are involved in hypercholesterolemia-induced leukocyte adhesion to vascular endothelium. This study assessed the contribution of interleukin 12 (IL-12) to these hypercholesterolemia-induced inflammatory responses. Intravital videomicroscopy was used to quantify leukocyte adhesion and emigration and oxidant stress (dihydrorhodamine oxidation) in unstimulated cremasteric venules (wall shear rate 
500 s–1) of wild-type (WT) C57Bl/6, lymphocyte-deficient [recombinase-activating gene knockout (RAG1–/–)], and IL-12-deficient (p35–/– and p40–/–; p35 and p40 are the two subunits of active IL-12) mice on either a normal (ND) or high-cholesterol (HC) diet for 2 wk. RAG1–/–-HC mice received splenocytes from WT-HC (WT 
RAG1–/–), p35–/–-HC (p35–/– RAG1–/–), or p40–/–-HC (p40–/– RAG1–/–) mice. Compared with WT-ND mice, WT-HC mice exhibited exaggerated leukocyte adherence and emigration as well as increased dihydrorhodamine oxidation. The enhanced leukocyte recruitment was absent in the RAG1–/–-ND, p35–/–-ND, and p40–/–-ND groups. Hypercholesterolemia-induced leukocyte adherence and emigration were attenuated in RAG1–/–-HC vs. WT-HC mice but were similar to ND mice. Furthermore, compared with WT-HC animals, p35–/–-HC and p40–/–-HC mice showed significantly lower leukocyte adhesion and tissue oxidant stress responses, but these values were comparable to ND mice. Leukocyte adherence and emigration in WT RAG1–/– mice were similar to responses of WT-HC mice. However, p35–/– RAG1–/– mice had lower levels of adherence and emigration vs. the WT RAG1–/– and WT-HC groups. Elevated levels of leukocyte adherence and emigration were restored by 
50% toward WT-HC levels in p40–/– RAG1–/– mice. These findings implicate IL-12 in the inflammatory responses observed in the venules of hypercholesterolemic mice.
endothelium; oxidative stress; lymphocytes
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