p110Delta Inhibits Monocyte Infiltration by Thioglycollate-Induced Periotoneal Inflammation but Not HCD-Induced Inflammation and Atherosclerosis in APOE KO Mice

卷:50

Tang, Futian ; Li, Xiaoqiang ; Gui, Yali ; Qi, Cuiling ; Lu, Meili ; Dai, Chunmei ; Wang, Hongxin ; Wang, Lijing

关键词: Phosphoinositide 3-kinase p110 delta;    Atherosclerosis;    Inflammation;    Leukocyte;    Monocyte;   

DOI  :  10.1007/s11745-015-4026-8

学科分类：食品科学和技术

【 摘 要 】

We have previously reported that phosphoinositide 3-kinase p110 delta knockout (p110 delta KO) diminished the adhesion of leukocytes to capillary venules and suppressed the peritoneal infiltration of leukocytes, both functions that play important roles in atherosclerosis. Therefore, we hypothesized that p110 delta deficiency might be protective against atherosclerosis. Apolipoprotein E knockout (ApoE KO) mice were crossed with p110 delta KO mice to generate homozygous double knockout mice (ApoE/p110 delta DKO). The present study showed that ApoE/p110 delta DKO mice fed with a high cholesterol diet (HCD) demonstrated less peritoneal infiltration of leukocytes and monocytes compared with ApoE KO mice after intraperitoneal injection of thioglycollate, an inducer of acute peritoneal inflammation. Unexpectedly, atherosclerosis in the aortic root and in the entire aorta was similar between the ApoE/p110 delta DKO and ApoE KO groups. No difference in Mac-3 expression, indicative of macrophage infiltration, was found between the two groups. Further analysis showed that ApoE KO mice chronically fed with HCD had increased levels of total cholesterol, low-density lipoprotein in the blood and counts and percentages of circulating monocytes compared with ApoE KO mice fed with a normal diet. Consistently, the deficiency of p110 delta affected neither the counts nor the percentages of monocytes nor the lipid profiles in the blood. The results suggested that p110 delta plays an important role in acute but not in chronic inflammation, the latter being included in the early characteristics of atherosclerosis, which might explain the finding that p110 delta deficiency fails to inhibit early atherosclerosis.