NDLI: Influence of oxidatively modified LDL on monocyte-macrophage differentiation

Content Provider	Springer Nature Link
Author	Radhika, Achuthan Jacob, Shiney S. Sudhakaran, Perumana R.
Copyright Year	2007
Abstract	Transendothelial migration of peripheral blood mononuclear cells (PBMCs) and their subsequent interaction with the subendothelial matrix lead to their differentiation to macrophages (mϕs). To study whether preexposure of monocytes in circulation to modified proteins influences their differentiation to mϕs, an in vitro model system using isolated PBMC in culture was used. The effect of modified proteins such as oxidatively modified LDL (ox-LDL), acetylated and non-enzymatically glycated-BSA (NEG-BSA) on the differentiation process was studied by monitoring the upregulation of mϕ specific functions such as endocytosis, production of matrix metalloproteinases (MMPs), expression of surface antigen, activity of β-glucuronidase and down regulation of monocyte specific myeloperoxidase activity. Rate of endocytosis, production of MMPs and β-glucuronidase activity were significantly greater in cells treated with modified proteins irrespective of the nature of modification. Both CuSO$_{4}$ ox-LDL and HOCl ox-LDL increased the rate of expression of the mϕ specific functions. FACS analysis showed that the rate of upregulation of mϕ specific CD71 and down regulation of monocyte specific CD14 were high in cells supplemented with modified proteins. Studies using PPARγ antagonist and agonist suggest its involvement in CuSO$_{4}$ ox-LDL induced monocyte-macrophage (mo-mϕ) differentiation whereas the expression of macrophage specific functions in cells exposed to other modified proteins was independent of PPARγ. PBMC isolated from hypercholesterolemic rabbits in culture expressed mϕ specific functions at a faster rate compared to normal controls indicating that these observations are relevant in vivo. These results indicate that preexposure of monocytes to modified proteins promote their differentiation to mϕs and may serve as a feed forward type control for clearing modified proteins.
Starting Page	133
Ending Page	143
Page Count	11
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	305
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2007-07-28
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Monocyte-macrophage differentiation PPAR γ Ox-LDL NEG-BSA Matrix metalloproteinases Endocytosis Cardiology Oncology Medical Biochemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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