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REVIEW: Mechanisms Determining Phenotypic Heterogeneity of Hepatocytes

I. F. Usynin* and L. E. Panin

Institute of Biochemistry, Siberian Division of the Russian Academy of Medical Sciences, ul. Akademika Timakova 2, 630117 Novosibirsk, Russia; fax: (383) 335-6811; E-mail: ivan.usynin@soramn.ru

* To whom correspondence should be addressed.

Received June 25, 2007; Revision received October 15, 2007
This review summarizes results of biochemical and immunohistochemical studies indicating the existence of functional heterogeneity of hepatocytes depending on their localization in the hepatic acinus; this determines characteristic features of metabolism of carbohydrates, lipids, and xenobiotics. The physiological significance of hepatocyte heterogeneity is discussed. According to the proposed model of intercellular communication, the metabolic specialization of hepatocytes is determined by secretory activity of hepatic resident macrophages (Kupffer cells) localized mainly in the periportal zone of the liver acinus. Macrophages participate in secretion of a wide spectrum of intercellular mediators (cytokines, prostaglandins, growth factors) and also in metabolism of numerous blood metabolites and biologically active substances (hormones, lipoproteins, etc.). In the sinusoid and in the space of Disse (also known as perisinusoidal space) they form a concentration gradient of regulatory factors and metabolites inducing the phenotypic differences between hepatocytes.
KEY WORDS: liver, metabolism, hepatocyte, heterogeneity, macrophage, Kupffer cell, intercellular communications

DOI: 10.1134/S0006297908040019