Collagen type I synthesized by pancreatic periacinar stellate cells (PSC) co-localizes with lipid peroxidation-derived aldehydes in chronic alcoholicpancreatitis

Chronic alcoholic pancreatitis (CAP) is characterized by progressive pancre atic fibrosis and loss of the acinar cell mass, but the pathogenesis of pan creatic fibrosis in the human is poorly understood. It has been recently su ggested that lipid peroxidation-derived aldehydes such as 4-hydroxynonenal (HNE) are involved in tissue damage and fibrosis in other organs. The aim o f this study was to evaluate the role of oxidative stress in the developmen t of alcohol-induced pancreatic fibrosis in humans, and to assess the contr ibution of pancreatic periacinar stellate cells (PSC) in the in vivo synthe sis of extracellular matrix components during CAP. Lipid peroxidation was e valuated in tissue specimens obtained from patients with CAP who underwent surgical procedures, by immunohistochemistry using a monoclonal antibody di rected against HNE-protein adducts, Immunohistochemical determination of co llagen type I, alpha-smooth muscle actin (a-SD;IA), and the beta subunit of human platelet-derived growth factor (PDGF-R beta) was also performed. In addition, the tissue mRNA expression of procollagen I, PDGF-R beta, and tra nsforming growth factor-beta 1 (TGF-beta 1) was evaluated by in situ hybrid ization, in CAP, increased formation of HNE-protein adducts was evident in acinar cells adjacent to the interlobular connective tissue that stained po sitively for collagen type I. HNE staining was absent in normal pancreas. S everal non-parenchymal periacinar cells (PSC) underlay the HNE-stained acin ar cells. Those PSC stained positively for cr-SMA and PDGF-R beta and showe d active synthesis of procollagen type I by in situ expression of the speci fic mRNAs. The pattern of expression of PDGF-R beta mRNA reflected that obs erved in immunostaining, showing increased amounts of transcripts in PSC, T GF-beta 1 mRNA expression was increased in CAP, but transcripts were found in several cell types including PSC, acinar, and ductal cells. These result s indicate that significant lipid peroxidation phenomena occur in CAP and t hat they are associated with active synthesis of collagen by PSC, Copyright (C) 2000 John Wiley & Sons, Ltd.