OJVM  Vol.2 No.3 , September 2012
Immunohistochemical Aspects of Ito and Kupffer Cells in the Liver of Domesticated and Wild Ruminants
Abstract: The mammalian liver is a morphologically and functionally complex organ, made up of not only of the largely predominant parenchymal cells (hepatocytes) but also non-parenchymal cells. Although there are less non-parenchymal cells than hepatocytes, they nevertheless play an important role in regulating many hepatocyte functions, as well as in the immunology of the liver. We investigated the structural aspects of the liver and the morpho-functional characteristics of Ito and Kupffer cells in two domesticated ruminant species (cattle and goat) in comparison with four wild ruminant species living in captivity in a zoo in northern Italy. The liver specimens were studied using histological, histochemical and immunohistochemical methods. The liver parenchyma was structurally normal. Immunohistochemistry was performed for desmin, glial fibrillary acidic protein (GFAP), vimentin, α-smooth muscle actin (α-SMA), collagen I, lysozyme, CD 68 and tumor necrosis factor α (TNF-α). In all the studied ruminants, Ito cells reacted with desmin and vimentin antibodies, Kupffer cells were evidenced only with lysozyme-immunopositivity, and both displayed a characteristic distribution in the hepatic lobular/acinar structure. The results obtained, not only contribute to the knowledge of ruminant wild species, but also help to define a normal structure reference for the diagnosis and treatment of liver diseases.
Cite this paper: V. Carollo, A. Di Giancamillo, F. Vitari, R. Schneider and C. Domeneghini, "Immunohistochemical Aspects of Ito and Kupffer Cells in the Liver of Domesticated and Wild Ruminants," Open Journal of Veterinary Medicine, Vol. 2 No. 3, 2012, pp. 129-136. doi: 10.4236/ojvm.2012.23022.

[1]   Z. Kmie?, “Cooperation of Liver Cells in Health and Disease,” Advances in Anatomy, Embryology and Cell Biology, Vol. 161, No. 1, 2001, pp. 1-151.

[2]   D. E. Malarkey, K. Johnson, L. Ryan, G. Boorman and R. R. Maronpot, “New Insights into Functional Aspects of Liver Morphology,” Toxicologic Pathology, Vol. 33, No. 1, 2005, pp. 27-34. doi:10.1080/01926230590881826

[3]   K. Uetsuka, S. Nishikawa, A. Yasoshima, H. Nakayama and K. Doi, “Histopathological Characteristics of Ito Cells and Kupffer Cells in the Feline Liver,” Journal of Veterinary Medical Science, Vol. 68, No. 3, 2006, pp. 235-242. doi:10.1292/jvms.68.235

[4]   A. M. Neyrinck, L. D. De Wispelaere, V. P. Vanhulle, H. S. Taper and N. M. Delzenne, “Are Kupffer Cells Involved in the Metabolic Adaptation of the Liver to Dietary Carbohydrates Given after Fasting?” Biochimica et Biophysica Acta—General Subjects, Vol. 1475, No. 3, 2000, pp. 238-244. doi:10.1016/S0304-4165(00)00070-2

[5]   G. A. Parker and C. A. Picut, “Liver Immunobiology,” Toxicologic Pathology, Vol. 33, No. 1, 2005, pp. 52-62. doi:10.1080/01926230590522365

[6]   G. A. Parker and C. A. Picut, “Immune Functions in Nonlymphoid Organs: The Liver,” Toxicology Pathology, Vol. 40, No. 2, 2011, pp. 237-247.

[7]   H. Senoo, N. Kojima and M. Sato, “Vitamin A-Storing Cells (Stellate Cells),” Vitamins and Hormones, Vol. 75, 2007, pp. 131-159. doi:10.1016/S0083-6729(06)75006-3

[8]   M. L. Hautekeete and A. Geerts, “The Hepatic Stellate (Ito) Cell: Its Role in Human Liver Disease,” Virchows Archiv, Vol. 430, No. 3, 1997, pp. 195-207. doi:10.1007/BF01324802

[9]   K. Iwaisako, D. A. Brenner and T. Kisseleva, “What’s New in Liver Fibrosis? The Origin of Myofibroblasts in Liver Fibrosis,” Journal of Gastroenterology and Hepatology, Vol. 27, No. 2, 2012, pp. 65-68. doi:10.1111/j.1440-1746.2011.07002.x

[10]   H. Senoo, K. Yoshikawa, M. Morii, M. Miura, K. Imai and Y. Meezaki, “Hepatic Stellate Cell (Vitamin A-Storing Cell) and Its Relative—Past, Present and Future,” Cell Biology International, Vol. 34, No. 12, 2010, pp. 1247-1272. doi:10.1042/CBI20100321

[11]   F. Tacke and R. Weiskirchen, “Update on Hepatic Stellate Cells: Pathogenic Role in Liver Fibrosis and Novel Isolation Techniques,” Expert Review of Gastroenterology and Hepathology, Vol. 6, No. 1, 2012, pp. 67-80. doi:10.1586/egh.11.92

[12]   M. Naito, G. Hasegawa, Y. Ebe and T. Yamamoto, “Dif- ferentiation and Function of Kupffer Cells,” Medical Electron Microscopy, Vol. 37, No. 1, 2004, pp. 16-28. doi:10.1007/s00795-003-0228-x

[13]   I. Kiki, B. Z. Altunkaynak, M. E. Altunkaynak, O. Vuraler, D. Unal and S. Kaplan, “Effect of High Fat Diet on the Volume of Liver and Quantitative Feature of Kupffer Cells in the Female Rat: A Stereological and Ultrastructural Study,” Obesity Surgery, Vol. 17, No. 10, 2007, pp. 1381-1388. doi:10.1007/s11695-007-9219-7

[14]   L. Bouwens, M. Baekeland, R. De Zanger and E. Wisse, “Quantitation, Tissue Distribution and Proliferation Kinetics of Kupffer Cells in Normal Rat Liver,” Hepatology, Vol. 6, No 4, 1986, pp.718-722. doi:10.1002/hep.1840060430

[15]   B. Borch-Iohnsen and K. Thorstensen, “Iron Distribution in the Liver and Duodenum during Seasonal Iron Overload in Svalbard Reindeer,” Journal of Comparative Pathology, Vol. 141, No. 1, 2009, pp. 27-40. doi:10.1016/j.jcpa.2009.02.001

[16]   P. Olias, A. T. Weiss, A. D. Gruber and R. Klopfleisch, “Iron Storage Disease in Red Deer (Cervus elaphus elaphus) Is Not Associated with Mutations in the HFE Gene,” Journal of Comparative Pathology, Vol. 145, No. 2-3, 2011, pp. 207-213. doi:10.1016/j.jcpa.2010.12.012

[17]   A. M. Neyrinck, S. Margagliotti, C. Gomez and N. M. Delzenne, “Kupffer Cell-Derived Prostaglandin E2 Is Involved in Regulation of Lipid Synthesis in Rat Liver Tissue,” Cell Biochemistry and Function, Vol. 22, No. 5, 2004, pp. 327-332. doi:10.1002/cbf.1110

[18]   H. Gordon and H. H. Sweet, “A Simple Method for the Silver Impregnation of Reticulin,” American Journal of Pathology, Vol. 12, No. 4, 1936, pp. 545-552.

[19]   K. Neubauer, T. Knittel, S. Aurisch, P. Fellmer and G. Ramadori, “Glial Fibrillary Acidic Protein—A Cell Type Specific Marker for Ito Cells in vivo and in vitro,” Journal of Hepatology, Vol. 24, No. 6, 1996, pp. 719-730. doi:10.1016/S0168-8278(96)80269-8

[20]   K. Uetsuka, S. Nishikawa, K. Isobe and H. Nakayama, “Histopathological Characteristics of Kupffer Cells and Ito Cells in the Porcine and Bovine Liver,” Journal of Veterinary Medical Science, Vol. 69, No. 7, 2007, pp. 767-770. doi:10.1292/jvms.69.767

[21]   S. Morini, S. Carotti, G. Carpino, A. Franchitto, S. G. Corradini, M. Merli and E. Gaudio, “GFAP Expression in the Liver as an Early Marker of Stellate Cells Activation,” Italian Journal of Anatomy and Embryology, Vol. 110, No. 4, 2005, pp. 193-207.

[22]   A. C. Bourque, I. C. Fuentealba, R. Bildfell, P. I. Daoust and P. Hanna, “Congenital Hepatic Fibrosis in Calves,” The Canadian Veterinary Journal, Vol. 42, No. 2, 2001, pp. 145-146.

[23]   M. B. Torres and K. I. Coelho, “Foamy Macrophages in the Liver of Cattle Fed Brachiaria Brizantha Hay,” Veterinary and Human Toxicology, Vol. 45, No. 3, 2003, pp. 163-164.

[24]   S. Haywood, T. Müller, A. M. Mackenzie, W. Müller, M. S. Tanner, P. Heinz-Erian, C. L. Williams and M. J. Loughran, “Copper-Induced Hepatotoxycosis with Hepatic Stellate Cells Activation and Severe Fibrosis in North Ronaldsay Lambs: A Model for Non-Wilsonian Hepatic Copper Toxicosis of Infants,” Journal of Comparative Pathology, Vol. 130, No. 4, 2004, pp. 266-277. doi:10.1016/j.jcpa.2003.11.005

[25]   K. Neubauer, B. Saile and G. Ramadori, “Liver Fibrosis and Altered Matrix Synthesis,” Canadian Journal of Gastroenterology, Vol. 15, No. 3, 2001, pp. 187-193.

[26]   N. R. Tomanovic, I. V. Boricic, D. C. Brasanac, Z. M. Stojsic, D. S. Delic and B. J. Brmbolic, “Activated Liver Stellate Cells in Chronic Viral C Hepatitis: Histopathological and Immunohistochemical Study,” Journal of Gastrointestinal and Liver Disease, Vol. 18, No. 2, 2009, pp. 163-167.

[27]   C. Ju, “The Role of Haptic Macrophages in Regulation of Idiosyncratic Drug Reactions,” Toxicology Pathology, Vol. 37, No. 1, 2009, pp. 12-17. doi:10.1177/0192623308329475

[28]   C. Liu, Q. Tao, M. Sun, J. Z. Wu, W. Yang, P. Jian, J. Peng, Y. Hu, C. Liu and P. Liu, “Kupffer Cells Are Associated with Apoptosis, Inflammation and Fibrotic Effects in Hepatic Fibrosis in Rats,” Laboratory Investigation; a journal of technical methods and pathology, Vol. 90, No. 12, 2010, pp. 1805-1816.

[29]   S. Kushibiki, “Tumor Necrosis Factor-α-Induced Inflammatory Response in Cattle,” Animal Science Journal, Vol. 82, No. 4, 2011, pp. 504-511. doi:10.1111/j.1740-0929.2011.00931.x

[30]   J. H. Lefkowitch, J. H. Haythe and N. Regent, “Kupffer cell Aggregation and Perivenular Distribution in Steatohepatitis,” Modern Pathology, Vol. 15, No 7, 2002, pp. 699-704. doi:10.1097/01.MP.0000019579.30842.96

[31]   J. Yamate, H. Yoshida, Y. Tsukamoto, M. Ide, M. Kuwamura, F. Ohashi, T. Miyamoto, T. Kotani, S. Sakuma and M. Takeya, “Distributiona of Cells Immunopositive for AM-3K, a Novel Monoclonal Antibody Recognizing Human Macrophages, in Normal and Diseased Tissues of Dogs, Cats, Horse, Cattle, Pigs, and Rabbits,” Veterinary Pathology, Vol. 37, No. 2, 2000, pp. 168-176. doi:10.1354/vp.37-2-168

[32]   P. Zelnickova, J. Matiasovic, B. Pavlova, H. Kudlackova, F. Kovaru and M. Faldyna, “Quantitative Nitric Oxide Production by Rat, Bovine and Porcine Macrophages,” Nitric Oxide: Biology and Chemistry, Vol. 19, No. 1, 2008, pp. 36-41.

[33]   P. F. Moore, “Characterization of Cytoplasmic Lysozyme Immunoreactiviry as a Histiocytic Marker in Normal Canine Tissue,” Veterinary Pathology, Vol. 23, No. 6, 1986, pp. 763-769.

[34]   G. L. Su, “Lipopolysaccharides in Liver Injury: Molecular Mechanisms of Kupffer Cell Activation,” American Journal of Physiology. Gastrointestinal and Liver Physiology, Vol. 283, No. 2, 2002, pp. G256-G265.

[35]   L. C. Kabaroff, A. Rodriguez, M. Quinton, H. Boermans and N. A. Karrow, “Assessment of the Ovine Acute Phase Response and Hepatic Gene Expression in Response to Escherichia Coli Endotoxin,” Veterinary Immunology and Immunopathology, Vol. 113, No. 1-2, 2006, pp. 113-124. doi:10.1016/j.vetimm.2006.04.003

[36]   S. J. Everest, A. M. Ramsay, M. J. Chaplin, S. Everitt, M. J. Stack, M. H. Neale, M. Jeffrey, S. J. Moore, S. J. Bellworthy and L. A. Terry, “Detection and Localization of Prp (Sc) in the Liver of the Sheep Infected with Scrapie and Bovine Spongiform Enecephalopathy,” PLoS One, Vol. 12, No. 5, 2011, p. e19737. doi:10.1371/journal.pone.0019737

[37]   M. Yoshioka, T. Ito, S. Miyazaki and Y. Nakajima, “The Release of Tumor Necrosis Factor-Alpha, Interleukin-1. Interleukin-6 and Prostaglandin E2 in Bovine Kupffer Cells Stimulated with Bacterial Lipopolysaccharide,” Veterinary Immunology and Immunopathology, Vol. 66, No. 3-4, 1998, pp. 301-307. doi:10.1016/S0165-2427(98)00206-2

[38]   D. Driemeier, E. M. Colodei, E. J. Gimeno and S. S. Barros, “Lysosomal Storage Disease Caused by Sida Carpinifolia Poisoning in Goats,” Veterinary Pathology, Vol. 37, No. 2, 2000, pp. 153-159. doi:10.1354/vp.37-2-153

[39]   A. G. Armién, C. H. Tokamia, P. V. Peixoto, J. D. Barbosa and K. Frese, “Clinical and Morphological Changes in Ewes and Fetusues Poisoned by Ipomea Carnea Subspecies Fistulosa,” Journal of Veterinary Diagnostic Investigation, Vol. 23, No. 2, 2011, pp. 221-232. doi:10.1177/104063871102300205

[40]   M. Yamada, M. Nakagawa, M. Haritani, M. Kobayashi, H. Furuoka and T. Matsui, “Histopathological Study of Experimental Acute Poisonong of Cattle by Autumn Crocus (Colchicum Autumnale L.),” Journal of Veterinary Medical Science, Vol. 60, No. 8, 1998, pp. 949-952. doi:10.1292/jvms.60.949

[41]   S. D. Stoev, N. Grozeva, R. Sieonov, I. Borisov, H. Hubenov, Y. Nikolov, M. Tsaneva and S. Lazarova, “Experimental Cadmium Poisoning in Sheep,” Experimental and Toxicologic Pathology, Vol. 55, No. 4, 2003, pp. 309-314. doi:10.1078/0940-2993-00333

[42]   E. C. Sleyster and D. L. Knook, “Relation between Localization and Function of Rat Liver Kupffer Cells,” Laboratory Investigation; a Journal of Technical Methods and Pathology, Vol. 47, No. 5, 1982, pp. 484-490.

[43]   R. R. Hofmann and D. R. M. Stewart, “Grazer or Browser: A Classification Based on the Stomach Structure and Feeding Habits of East African Ruminants,” Mammalia, Vol. 36, No. 2, 1972, pp. 226-240. doi:10.1515/mamm.1972.36.2.226

[44]   T. J. Hackmann and J. N. Spain, “Invited Review: Ruminant Ecology and Evolution: Perspectives Useful to Ruminant Livestock Research and Production,” Journal of Dairy Science, Vol. 93, No. 4, 2010, pp. 1320-1334. doi:10.3168/jds.2009-2071