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1 Department of Molecular and Cellular Physiology, Louisiana State University, Health Sciences Center, Shreveport, LA, USA
* To whom correspondence should be addressed. E-mail: dgrang{at}lsuhsc.edu.
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 (DHR) oxidation) in unstimulated cremasteric venules (WSR
500/s) of wild-type C57Bl/6 (WT), lymphocyte-deficient (RAG1-/-), and IL-12-deficient (p35-/- and p40-/-) 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. WT-HC mice, vs WT-ND, exhibited exaggerated leukocyte adherence and emigration as well as increased DHR oxidation. The enhanced leukocyte recruitment was absent in RAG1-/--ND, p35-/--ND and p40-/--ND groups. Hypercholesterolemia-induced leukocyte adherence and emigration were attenuated in RAG1-/--HC vs WT-HC, but similar to ND mice. Furthermore, p35-/--HC and p40-/--HC mice, vs WT-HC animals, showed significantly lower leukocyte adhesion and tissue oxidant stress responses, but comparable to ND mice. Leukocyte adherence and emigration in WTRAG1-/- were similar to WT-HC responses. However, p35-/-RAG1-/- mice had lower levels of adherence and emigration vs WTRAG1-/- and WT-HC groups. Elevated levels of leukocyte adherence and emigration were restored by approximately 50% towards WT-HC levels in p40-/-RAG1-/- mice. These findings implicate IL-12 in the inflammatory responses observed in venules of hypercholesterolemic mice.
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