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

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Lipids

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.

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Abbreviations

ApoE KO:

Apolipoprotein E knockout

DBA:

3′, 3′-Diaminobenzidine

HCD:

High cholesterol diet

HDL-C:

HDL cholesterol

IPP:

Image-Pro Plus

LDL:

Low-density lipoprotein

LDL-C:

LDL cholesterol

ND:

Normal diet

oxLDL:

Oxidatively modified low-density lipoprotein

p110δ KO:

Phosphoinositide 3-kinase p110δ knockout

PBS:

Phosphate-buffered saline

PI3K:

Phosphoinositide 3-kinase

TAG:

Triacylglycerol

TBARS:

Thiobarbituric acid reactive substances

TC:

Total cholesterol

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Acknowledgments

This work was supported by the Natural Science Foundation of China (no. 30871304), the Natural Science Foundation of China (no. 81374008) and the Talent Fund of Liaoning Medical University (no. 2014-18).

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Key Laboratory of Cardio- and Cerebro-vascular Drug, Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, 121001, China

    Futian Tang, Meili Lu, Chunmei Dai & Hongxin Wang

  2. Institute of Vascular Biology Research, Guangdong Pharmaceutical University, Guangzhou, 510006, China

    Xiaoqiang Li, Yali Gui, Cuiling Qi & Lijing Wang

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  1. Futian Tang
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  2. Xiaoqiang Li
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  6. Chunmei Dai
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  7. Hongxin Wang
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  8. Lijing Wang
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Correspondence to Lijing Wang.

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Tang, F., Li, X., Gui, Y. et al. p110Delta Inhibits Monocyte Infiltration by Thioglycollate-Induced Periotoneal Inflammation but Not HCD-Induced Inflammation and Atherosclerosis in APOE KO Mice. Lipids 50, 839–846 (2015). https://doi.org/10.1007/s11745-015-4026-8

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  • DOI: https://doi.org/10.1007/s11745-015-4026-8

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