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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Aug;90(2):642–646. doi: 10.1172/JCI115905

Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients.

M Pinzani 1, P Failli 1, C Ruocco 1, A Casini 1, S Milani 1, E Baldi 1, A Giotti 1, P Gentilini 1
PMCID: PMC443145  PMID: 1644929

Abstract

Liver perisinusoidal fat-storing cells (FSC) show morphological and ultrastructural characteristics similar to pericytes regulating local blood flow in other organs. In the present study we have analyzed whether FSC respond to local vasoconstrictors such as thrombin, angiotensin-II, and endothelin-1 with an increase in intracellular free calcium concentration ([Ca2+]i) coupled with effective cell contraction. All agonists tested induced a rapid and dose-dependent increase in [Ca2+]i followed by a sustained phase lasting several minutes in confluent monolayers of Fura-2-loaded human FSC. Pharmacological studies performed using different Ca2+ channel blockers indicated that, at least for thrombin and angiotensin-II, the sustained phase is due to the opening of voltage-sensitive membrane Ca2+ channels. To analyze the temporal and spatial dynamics of Ca2+ release in response to these agonists, we performed experiments on individual Fura-2-loaded human FSC using a dual wavelength, radiometric video imaging system. The rise in [Ca2+]i was exclusively localized to the cytoplasm, particularly in the branching processes. Increases in [Ca2+]i more than four-fold were associated with a simultaneous and transient reduction of cell area indicating reversible cell contraction. Our results indicate that the Ca(2+)-dependent contraction of human FSC in vitro may reflect a potential role in regulating sinusoidal blood flow in vivo.

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  1. Bhathal P. S., Grossman H. J. Reduction of the increased portal vascular resistance of the isolated perfused cirrhotic rat liver by vasodilators. J Hepatol. 1985;1(4):325–337. doi: 10.1016/s0168-8278(85)80770-4. [DOI] [PubMed] [Google Scholar]
  2. Blomhoff R., Wake K. Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis. FASEB J. 1991 Mar 1;5(3):271–277. doi: 10.1096/fasebj.5.3.2001786. [DOI] [PubMed] [Google Scholar]
  3. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  4. Friedman S. L., Roll F. J. Isolation and culture of hepatic lipocytes, Kupffer cells, and sinusoidal endothelial cells by density gradient centrifugation with Stractan. Anal Biochem. 1987 Feb 15;161(1):207–218. doi: 10.1016/0003-2697(87)90673-7. [DOI] [PubMed] [Google Scholar]
  5. Galizzi J. P., Borsotto M., Barhanin J., Fosset M., Lazdunski M. Characterization and photoaffinity labeling of receptor sites for the Ca2+ channel inhibitors d-cis-diltiazem, (+/-)-bepridil, desmethoxyverapamil, and (+)-PN 200-110 in skeletal muscle transverse tubule membranes. J Biol Chem. 1986 Jan 25;261(3):1393–1397. [PubMed] [Google Scholar]
  6. Geerts A., Vrijsen R., Rauterberg J., Burt A., Schellinck P., Wisse E. In vitro differentiation of fat-storing cells parallels marked increase of collagen synthesis and secretion. J Hepatol. 1989 Jul;9(1):59–68. doi: 10.1016/0168-8278(89)90076-7. [DOI] [PubMed] [Google Scholar]
  7. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  8. Kreisberg J. I., Venkatachalam M., Troyer D. Contractile properties of cultured glomerular mesangial cells. Am J Physiol. 1985 Oct;249(4 Pt 2):F457–F463. doi: 10.1152/ajprenal.1985.249.4.F457. [DOI] [PubMed] [Google Scholar]
  9. Mak K. M., Lieber C. S. Lipocytes and transitional cells in alcoholic liver disease: a morphometric study. Hepatology. 1988 Sep-Oct;8(5):1027–1033. doi: 10.1002/hep.1840080508. [DOI] [PubMed] [Google Scholar]
  10. Mené P., Simonson M. S., Dunn M. J. Physiology of the mesangial cell. Physiol Rev. 1989 Oct;69(4):1347–1424. doi: 10.1152/physrev.1989.69.4.1347. [DOI] [PubMed] [Google Scholar]
  11. Nakano M., Worner T. M., Lieber C. S. Perivenular fibrosis in alcoholic liver injury: ultrastructure and histologic progression. Gastroenterology. 1982 Oct;83(4):777–785. [PubMed] [Google Scholar]
  12. Neylon C. B., Hoyland J., Mason W. T., Irvine R. F. Spatial dynamics of intracellular calcium in agonist-stimulated vascular smooth muscle cells. Am J Physiol. 1990 Oct;259(4 Pt 1):C675–C686. doi: 10.1152/ajpcell.1990.259.4.C675. [DOI] [PubMed] [Google Scholar]
  13. Pinzani M., Abboud H. E., Gesualdo L., Abboud S. L. Regulation of macrophage colony-stimulating factor in liver fat-storing cells by peptide growth factors. Am J Physiol. 1992 Apr;262(4 Pt 1):C876–C881. doi: 10.1152/ajpcell.1992.262.4.C876. [DOI] [PubMed] [Google Scholar]
  14. Pinzani M., Gesualdo L., Sabbah G. M., Abboud H. E. Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. J Clin Invest. 1989 Dec;84(6):1786–1793. doi: 10.1172/JCI114363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pinzani M., Knauss T. C., Pierce G. F., Hsieh P., Kenney W., Dubyak G. R., Abboud H. E. Mitogenic signals for platelet-derived growth factor isoforms in liver fat-storing cells. Am J Physiol. 1991 Mar;260(3 Pt 1):C485–C491. doi: 10.1152/ajpcell.1991.260.3.C485. [DOI] [PubMed] [Google Scholar]
  16. Poenie M., Alderton J., Steinhardt R., Tsien R. Calcium rises abruptly and briefly throughout the cell at the onset of anaphase. Science. 1986 Aug 22;233(4766):886–889. doi: 10.1126/science.3755550. [DOI] [PubMed] [Google Scholar]
  17. Ramadori G. The stellate cell (Ito-cell, fat-storing cell, lipocyte, perisinusoidal cell) of the liver. New insights into pathophysiology of an intriguing cell. Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;61(3):147–158. doi: 10.1007/BF02890417. [DOI] [PubMed] [Google Scholar]
  18. Ramadori G., Veit T., Schwögler S., Dienes H. P., Knittel T., Rieder H., Meyer zum Büschenfelde K. H. Expression of the gene of the alpha-smooth muscle-actin isoform in rat liver and in rat fat-storing (ITO) cells. Virchows Arch B Cell Pathol Incl Mol Pathol. 1990;59(6):349–357. doi: 10.1007/BF02899424. [DOI] [PubMed] [Google Scholar]
  19. Schmitt-Gräff A., Krüger S., Bochard F., Gabbiani G., Denk H. Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. Am J Pathol. 1991 May;138(5):1233–1242. [PMC free article] [PubMed] [Google Scholar]
  20. Shultz P. J., Knauss T. C., Mené P., Abboud H. E. Mitogenic signals for thrombin in mesangial cells: regulation of phospholipase C and PDGF genes. Am J Physiol. 1989 Sep;257(3 Pt 2):F366–F374. doi: 10.1152/ajprenal.1989.257.3.F366. [DOI] [PubMed] [Google Scholar]
  21. Simonson M. S., Dunn M. J. Endothelin-1 stimulates contraction of rat glomerular mesangial cells and potentiates beta-adrenergic-mediated cyclic adenosine monophosphate accumulation. J Clin Invest. 1990 Mar;85(3):790–797. doi: 10.1172/JCI114505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Somlyo A. V., Bond M., Somlyo A. P., Scarpa A. Inositol trisphosphate-induced calcium release and contraction in vascular smooth muscle. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5231–5235. doi: 10.1073/pnas.82.15.5231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wacker H. H., Hansmann M. L., Lumbeck H., Radzun H. J., Parwaresch M. R. Ein neuer Pan-Makrophagen Antikörper Ki-M1P erkennt plasmozytoide Lymphknotenzellen in Paraffinschnitten. Verh Dtsch Ges Pathol. 1990;74:159–164. [PubMed] [Google Scholar]
  24. Wake K. Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol. 1980;66:303–353. doi: 10.1016/s0074-7696(08)61977-4. [DOI] [PubMed] [Google Scholar]

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