Altered Acinar Distribution of Glutamine Synthetase and Different Growth Response of Cultured Enzyme-positive and -negative Hepatocytes after Partial Hepatectomy¹ Free

Partial hepatectomy (PH) results in the persistent drop of the specific activity of glutamine synthetase (GS) (EC 6.3.1.2). This drop correlates with the reduced proportion of GS⁺ hepatocytes and with the reduced GS⁺ area surrounding the central veins such that GS⁺ hepatocytes are arranged in a single cell layer only.

Cultivation of hepatocytes isolated at various times after PH revealed considerable differences in the growth characteristics of GS⁺ and GS⁻ hepatocytes discriminated by immunocytochemistry. In the absence or presence of epidermal growth factor and insulin, the labeling index of GS⁻ hepatocytes peaked in cultures established 48 h after PH at 10% and 50%, respectively, while that of GS⁺ cells was much lower (2% and 6%). In cultures established at later times after PH the labeling index of GS⁻ cells decreased gradually, while that of GS⁺ hepatocytes increased continuously, reaching about 20% and more than 50% for controls and epidermal growth factor/insulin-treated cultures, respectively, in cultures established 72 after PH. Norepinephrine stimulated the labeling index of both cell populations during the first 24 h only, but again GS^- hepatocytes responded somewhat earlier than did GS⁺ hepatocytes. These results demonstrate that the differences in the growth characteristics of GS⁺ and GS⁻ hepatocytes are due to different priming of these cells in vivo and may result in the different expansion of the respective cell populations during regeneration after PH.