Functional analysis of mouse hepatocytes differing in DNA content: volume, receptor expression, and effect of IFNgamma.
Polyploidy and binuclearity are characteristics of the mammalian liver. Increasing polyploidisation occurs with age and after administration of various drugs and chemicals. This study was designed to examine the function of ploidy by addressing several questions: (1) Does the increase in size of polyploid hepatocytes have any physiological function by altering surface receptor expression such as intercellular adhesion molecule-1 (ICAM-1, CD54) or IFNgammaR? and (2) Do polyploid cells respond differently to inflammatory cytokines such as interferon gamma (IFNgamma)? We have developed a method to accurately measure the volume of live isolated hepatocytes using confocal microscopy and image analysis. Using flow cytometry, we have shown that the expression of ICAM-1 increases with increasing DNA content and IFNgammaR is not detectable on isolated mouse hepatocytes. Diploid (2n), tetraploid (4n) and octoploid (8n) hepatocytes were found to be equally susceptible to IFNgamma-induced apoptosis in vitro. Although the function of polyploidy remains unanswered, we have described some of the characteristics of polyploidy in isolated hepatocytes and in vitro.
Martin
Nicola C
NC
Department of Pathology, University of Edinburgh, Medical School, United Kingdom.
McCullough
Christian T
CT
Bush
Peter G
PG
Sharp
Linda
L
Hall
Andrew C
AC
Harrison
David J
DJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D048429:Cell Size / Q000187:drug effects / Q000235:genetics; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006505:Hepatitis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011123:Polyploidy; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism; D000096743:Interferon gamma Receptor
D004247:DNA; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor