NDLI: Monocyte-macrophage differentiation in vitro: Modulation by extracellular matrix protein substratum

Content Provider	Springer Nature Link
Author	Jacob, Shiney Susan Shastry, Padma Sudhakaran, P.R.
Copyright Year	2002
Abstract	The influence of extracellular matrix (ECM) on monocyte-macrophage (mo-mφ) differentiation was investigated using an in vitro model with human peripheral blood mononuclear cells (PBMC) maintained on different matrix protein substrata. Macrophage specific markers associated with differentiation studied were, (a) endocytosis of modified proteins; (b) appearance of mφ specific matrix metalloproteinases (MMPs); (c) activities of myeloperoxidase (MPO) and β-D-glucuronidase; (d) changes in the expression of cell surface antigens. As the duration of monocytes in culture increased, a progressive increase in the rate of differentiation was seen as evidenced by mφ specific functions such as endocytosis of $^{125}$[I] acetyl BSA and the appearance of gelatinases A and B. Significantly higher rate of endocytosis and production of MMPs were found in monocytes maintained on fibronectin (FN) and COL I than on COL IV (FN > COL I > COL IV) indicating that cells in contact with stromal components differentiate at a faster rate. FACS analysis done on cells maintained in vitro for phenotypic profile characteristic to mo-mφ differentiation showed downregulation of CD14 occurring in a substratum dependent manner viz, (FN > COL IV > COL I) and upregulation of CD71 was high in cells maintained on COL I and COL IV. Intracellular enzymatic activities such as MPO significantly decreased irrespective of matrix substrata, while β-D-glucuronidase activity increased in a substratum dependent manner (FN > COL I > COL IV). Pretreatment of cells with genistein significantly decreased the secretion of MMPs, particularly MMP 9 in cells maintained on ECM protein (FN) indicating a phosphorylation dependent signalling process in mediating matrix effect. The results of these in vitro studies on mφ specific markers suggest that apart from the diffusible factors, the microenvironment as provided by various matrix proteins particularly FN can modulate mo-mφ differentiation.
Starting Page	9
Ending Page	17
Page Count	9
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	233
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2002-01-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cardiology Medical Biochemistry Oncology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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