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Recent reports have implicated liver non-parenchymal cells in liver injury as they can secrete; pro-inflammatory cytokines, excessive matrix proteins during fibrosis, and have been shown to initiate local immune responses [1-3]. Of the non-parenchymal cells, sinusoidal liver endothelial cells (SLECs) have been suggested to be a major contributor to the inflammatory processes observed in alcoholic liver disease (ALD) [4]. This is because SLECs are involved in the recruitment of leukocytes into the liver following the activation of an immune response, such as that observed in alcoholic hepatitis [4]. This process involves the release of cytokines TNF-alpha and IL-1beta, which increases the expression of adhesion molecules on the surface of SLECs and the release of chemokines (MIP-2 or MCP-1), which recruit leukocytes into the liver from the circulation [5,6]. These chemokines cause increased binding of leukocytes to the vessel walls and promote the trans-migration of these immune cells across the SLECs by the process of diapedesis [7,8].  Recent studies have shown that proteins can be modified by the metabolites of chronic ethanol consumption. Two of these metabolites, malondialdehyde (MDA) and acetaldehyde (AA), have been shown to synergistically bind to proteins (adduct) to form a product termed MAA [9]. This results in the binding and degradation of the adducted protein. However, chronic ethanol consumption decreases their degradation, but not the binding of these MAA modified proteins. Thus, the extended presence and binding of the MAA-modified proteins to their appropriate receptors could result in the induction of some biological response. It is thought that since these adducts are chronically present, a potential inflammatory response may be initiated similar to that observed in chronic viral infections. Additionally, observation of SLECs when exposed to MAA-Alb showed morphological changes in these cells that was suggestive of cell death (personal observation). Preliminary studies suggested that these changes may be due to TNF-alpha secretion by SLECs. Thus, it was the purpose of these experiments to begin assessing whether MAA-modified proteins can activate SLECs.

Malondialdehyde-acetaldehyde (MAA) modified proteins induce pro-inflammatory and pro-fibrotic responses by liver endothelial cells.