Acute inflammation of any etiology initiates a well recognized sequence of molecular and cellular changes within an organism. Included in this response is an alteration the synthesis and secretion of a number of hepatically derived plasma proteins. We have recently demonstrated that monocytes and macrophages, when activated, secrete a protein factor which significantly effects the synthesis of several hepatocyte derived plasma proteins. The long range objective of this proposal is (a) to isolate and chemically characterize this regular protein, (b) to understand what triggers the synthesis of the regulator in the monocyte and (c) to determine how the regulator protein stimulates the hepatic production of certain plasma proteins. A number of these studies will be carried out using hepatocytes and monocytes in monolayer culture systems. We have already established that primary hepatocytes in culture respond to the monocytic factor in a manner analogous to in vivo response. Furthermore, we have developed a specific quantitative bioassay which will be used to purify the hepatic stimulating factor. Results from these studies will provide new information on the chemistry and mode of action of an important regulator protein that is intimately involved in the acute inflammatory reaction. Since an acute inflammatory reaction occurs as a result of a number of trauma and disease states, knowledge of the chemistry and function of the factor(s) involved in causing the response is crucial to understanding the molecular mechanism of inflammation.
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| Otto, J M; Grenett, H E; Fuller, G M (1987) The coordinated regulation of fibrinogen gene transcription by hepatocyte-stimulating factor and dexamethasone. J Cell Biol 105:1067-72 |
| Fuller, G M; Bunzel, R J; Woloski, B M et al. (1987) Isolation of hepatocyte stimulating factor from human monocytes. Biochem Biophys Res Commun 144:1003-9 |
| Nham, S U; Fuller, G M (1986) Effect of fibrinogen degradation products on production of hepatocyte stimulating factor by a macrophage cell line (P388D1). Thromb Res 44:467-75 |
