The possible role of macrophages in transient hepatic fibrogenesis induced by acute carbon tetrachloride injury

Inhibition of 5‐lipoxygenase induces cell growth arrest and apoptosis in rat Kupffer cells: implications for liver fibrosis

“…The presence of an increased number of Kupffer cells together with the bulk release of inflammatory mediators by these hepatic macrophages is critical during the early inflammatory stages leading to liver fibrosis (Fig. 8) (4, 6–9). Whether this phenomenon is the result of the proliferation of Kupffer cells or the differentiation of recruited monocytes into Kupffer cells is at present unknown.…”

“…The population of Kupffer cells is self-renewing under steady-state conditions (5). However, during the onset of liver fibrosis, when inflammation is extensive, the population of liver resident macrophages increases exponentially (4)(5)(6)(7)(8)(9). Indeed, during the early stages of experimental liver disease induced by administration of carbon tetrachloride (CCl 4 ) to rats, an animal model that closely reproduces human liver disease (10), the number of Kupffer cells increases sharply (6)(7)(8)(9).…”

New Insights into the Regulation of Liver Inflammation and Oxidative Stress

“…Since activation of Kupffer cells and the subsequent release of potent proinflammatory mediators is considered to be an early step in the pathogenesis of liver damage and tissue remodeling, modulation of these cells provides a potential therapeutic strategy in liver disease. In fact, the number of macrophages is consistently increased and closely correlates with the degree of hepatic injury in experimental models of liver disease [133][134][135][136]. In these models, the degree of steatosis, inflammation, necrosis and collagen content is significantly attenuated by depletion of Kupffer cells by treatment with gadolinium chloride [137][138][139][140].…”

Review

“…· It is likely that perisinusoidal fibrosis makes a major contribution to the elinical consequences of fibrosis; it hinders the systemic functions of hepatocytes and non-parenchymal cells by development of diffusion barriers and/or it interferes with the portal haemodynamics due to Stenosis of intrasinusoidal blood flow and other disturbances of hepatic micfocifcülation (12) Epidermal growth factor f l Inhibition. In contrast to other tissues, the fibrogenic response is unnecessary for complete recovery of damaged liver (13), since the high regenerative capacity of hepatocytes (14) can substitute completely and rapidly for the necrotic parenchyma. In the late, dry phase tbe iricreased deposilion of extracelJular matrix leads to blood shunting around the liver and increased diffusion barriers resulting in parenchynial cell necrosis due to malnutrition.…”