In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 285, No. 6 ( 2003-12), p. H2623-H2629
Abstract:
We have previously shown that T lymphocytes and interferon-γ 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.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00566.2003
Language:
English
Publisher:
American Physiological Society
Publication Date:
2003
detail.hit.zdb_id:
603838-4
detail.hit.zdb_id:
1477308-9
SSG:
12
