title: p110Delta Inhibits Monocyte Infiltration by Thioglycollate-Induced Periotoneal Inflammation but Not HCD-Induced Inflammation and Atherosclerosis in APOE KO Mice.
abstract: We have previously reported that phosphoinositide 3-kinase p110δ knockout (p110δ 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 p110δ deficiency might be protective against atherosclerosis. Apolipoprotein E knockout (ApoE KO) mice were crossed with p110δ KO mice to generate homozygous double knockout mice (ApoE/p110δ DKO). The present study showed that ApoE/p110δ 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/p110δ 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 p110δ affected neither the counts nor the percentages of monocytes nor the lipid profiles in the blood. The results suggested that p110δ 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 p110δ deficiency fails to inhibit early atherosclerosis.
authors.affiliation: Key Laboratory of Cardio- and Cerebro-vascular Drug, Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Futian
authors.initials: F
authors.lastname: Tang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Li
authors.forename: Yali
authors.initials: Y
authors.lastname: Gui
authors.forename: Cuiling
authors.initials: C
authors.lastname: Qi
authors.forename: Meili
authors.initials: M
authors.lastname: Lu
authors.forename: Chunmei
authors.initials: C
authors.lastname: Dai
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
authors.forename: Lijing
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D058534:Class I Phosphatidylinositol 3-Kinases; D059305:Diet, High-Fat; D007249:Inflammation / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D010537:Peritoneum / Q000473:pathology*; D064029:Peroxisomal Multifunctional Protein-2 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D013864:Thioglycolates / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D002784:Cholesterol; D058534:Class I Phosphatidylinositol 3-Kinases; D064029:Peroxisomal Multifunctional Protein-2; D019869:Phosphatidylinositol 3-Kinases; D013864:Thioglycolates; C491288:Hsd17b4 protein, mouse; C421683:Pik3cd protein, mouse