Untitled

Abstract

The influence of extracellular matrix (ECM) on monocyte-macrophage (mo-mphi) 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 mphi specific matrix metalloproteinases (MMPs); (c) activities of myeloperoxidase (MPO) and beta-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 mphi 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-mphi 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 beta-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 mphi specific markers suggest that apart from the diffusible factors, the microenvironment as provided by various matrix proteins particularly FN can modulate mo-mphi differentiation.

Interleukin-13 Receptor α1-Dependent Responses in the Intestine Are Critical to Parasite Clearance

“…bakeri infection is associated with an increase in mucosal mast cell (MMC) numbers (29). IL-13 increased expression of PAR-2, a receptor for tryptase and trypsin that is linked to increased epithelial permeability (30). In WT mice, Hb1 infection increased murine mast cell protease-1 (mMCP-1) expression, with a further elevation following Hb2 infection, consistent with previous reports (3,27,28).…”

“…Our data confirm that the type2 IL-4R does not play a major role in the influx of MMC during Hb2 infection. Proteolytic cleavage of PAR-2 by mast-cell-derived serine proteases enhances epithelial permeability (30). We showed previously that nematode-induced upregulation of PAR-2 expression was STAT6 dependent (41).…”

Changes on lysosomal compartment during PMA-induced differentiation of THP-1 monocytic cells: Influence of type I and type IV collagens

“…The interaction with matrix components can contribute to regulating monocyte and macrophage behaviour, as suggested by previous studies [19,26] examining the role of signals mediated through matrix receptors, such as integrins [27,28]. For many cell types, integrin-mediated adhesion to matrix is required to proceed normally through the G1 phase of the cell cycle [28,29].…”

Fibronectin promotes the phorbol 12-myristate 13-acetate-induced macrophage differentiation in myeloid leukemia cells

“…Also, HL60 myeloid leukemia cells bind to fibronectin via a4b1 and a5b1 integrin heterodimers [6,7]. The signals provided by extracellular matrix potently influence the differentiation of normal monocytic cells into functional macrophages [8]. Correspondingly, in the current study, we hypothesized that adhesion of myeloid leukemia cells to fibronectin prior to PMA treatment may enhance macrophage differentiation.…”