The overall goal of the proposed work is to study the interactions between cultured monocytes/macrophages and vascular smooth muscle cells; specifically to monitor changes in the quantity and quality of smooth muscle cell collagen and elastin in response to perturbation by macrophages, and to measure the effect of smooth muscle cells and their extracellular matrix proteins on the production of a macrophage derived growth factor (MDGF). To accomplish this goal, smooth muscle cells will be cultured in the presence of macrophages and/or their secreted products. Measurements of the content of collagen and elastin produced by the smooth muscle cells in the presence and absence of macrophage products will be determined. Among the parameters that will be varied are number monocytes, growth state of the smooth muscle cells and the extent of matrix formation prior to the addition of monocytes and/or their secreted products. The results of this study should facilitate determination of whether monocyte products can alter the collagen and elastin produced by smooth muscle cells, and whether such changes are related to the proliferative state of the smooth muscle cells and/or the amount of matrix accumulated by the cultured smooth muscle cells. The effect of smooth muscle cells on MDGF production by monocytes will be monitored by culturing monocytes in the presence of smooth muscle cells and their secreted proteins. In addition, monocytes will be cultured on gels containing various concentrations and ratios of collagen and elastin to assess the effect of the purified proteins on MDGF production. As part of these studies, attempts to further purify MDGF will be made. The results of these studies may be of interest in understanding cell-cell reactions in general, since it represents an attempt to investigate smooth muscle growth and production of extracellular matrix proteins, and monocyte production of MDGF in an integrated fashion. They may also be relevant to events that occur in vivo in the maturation of monocytes to macrophages and in the development of atherosclerosis. In the process of diapedesis, monocytes encounter the vessel wall, which contains extracellular matrix proteins. Atherosclerosis is a disease that occurs in the large elastic vessels and is manifested by smooth muscle cell hyperplasia, an accumulation of collagen and elastin and the presence of macrophage-like cells. Therefore, the proposed work may serve as a simplified model for the development of atherosclerosis.
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| Kaufmann, J; Jorgensen, R W; Martin, B M et al. (1990) Monocyte activation by smooth muscle cell-derived matrices. Atherosclerosis 85:113-25 |
| Schreiber, B M; Martin, B M; Hollander, W et al. (1988) beta-VLDL-induced alterations in growth potentiating activity produced by mononuclear phagocytes. Atherosclerosis 69:69-79 |
