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Further studies on the relationship between drug-induced mast-cell secretion and local cell proliferation
Abstract:
A single intraperitoneal injection of Compound 48/80 in rats causes mast cell activation which is followed by a proliferation in fibroblasts and mesothelial cells in the mesentery. The same is true of organ-cultured rat mesentery, but in cultured guinea-pig mesentery Compound 48/80 has no morphological effects on mast cells and does not induce proliferation. The relationship between mast-cell secretion and cell proliferation in surrounding cells was studied further in the investigation now presented. Proliferation was estimated (a) by cytophotometric Feulgen DNA measurements in individual fibroblast and mesothelial cell nuclei; (b) by measurements of incorporation of 3H-TdR into DNA; (c) and by estimation of mitotic frequency. Mast-cell secretion was studied morphologically and by biochemical quantitation of histamine release. Compound 48/80 is a potent mast cell activator in the rat, stimulating mast cells to secretion. The results of this study suggest that Polymyxin B, another powerful mast-cell activator, apparently chemically unrelated to Compound 48/80, also stimulates the mesenterial cells to proliferation in the rat. In the guinea-pig Compound 48/80 does not induce mast-cell secretion or proliferation in fibroblasts and mesothelial cells in the mesentery. The results give further evidence that the cell proliferation induced by Compound 48/80 and Polymyxin B in rat mesentery is causally related to mast-cell secretion.
Insights
Compound 48/80 activates rat mast cells, causing fibroblast and mesothelial cell proliferation in the mesentery. This study confirms mast cell secretion is causally linked to this cell proliferation, a phenomenon not observed in guinea pigs.
Area of Science:
- Cell Biology
- Immunology
- Histology
Background:
- Compound 48/80 induces mast cell activation and subsequent fibroblast and mesothelial cell proliferation in rat mesentery.
- This effect is species-specific, as Compound 48/80 does not affect mast cells or induce proliferation in guinea-pig mesentery.
- The study investigates the causal relationship between mast cell secretion and surrounding cell proliferation.
Purpose of the Study:
- To further elucidate the relationship between mast cell secretion and the proliferation of adjacent fibroblasts and mesothelial cells.
- To investigate the role of mast cell activators, Compound 48/80 and Polymyxin B, in inducing mesothelial and fibroblast proliferation in rats.
- To compare the effects of Compound 48/80 on mast cells and mesothelial cells in rats versus guinea pigs.
Main Methods:
- Mast cell secretion was assessed morphologically and via biochemical histamine release quantification.
- Cell proliferation was measured using cytophotometric Feulgen DNA analysis, 3H-TdR incorporation into DNA, and mitotic frequency estimation.
- Experiments were conducted on both live rats and organ-cultured rat and guinea-pig mesentery.
Main Results:
- Compound 48/80 effectively activates rat mast cells, leading to secretion and subsequent proliferation of mesothelial and fibroblast cells.
- Polymyxin B, a chemically distinct mast cell activator, also induced mesothelial and fibroblast proliferation in rat mesentery.
- Compound 48/80 did not induce mast cell secretion or proliferation in guinea-pig mesentery, confirming species specificity.
Conclusions:
- Mast cell secretion is causally linked to the proliferation of fibroblasts and mesothelial cells in rat mesentery.
- The findings provide further evidence supporting the role of mast cell mediators in regulating connective tissue cell proliferation.
- The study highlights the differential response of rat and guinea-pig mesentery to mast cell activation by Compound 48/80.