Abstract
The structural and functional heterogeneity of hepatocytes and non-parenchymal cells across the liver lobule or acinus has been well documented. The geographic distribution and potential for induced expression of adhesion molecules on murine hepatic microvascular cells has not been reported, although these molecules are able to influence the metastatic outcome of intravascular cancer cells. We have postulated that the expression of adhesion molecules on these cells is susceptible to regulation by environmental factors and that these molecules have a zonal distribution across the acinus. To test this hypothesis, we injected C57BL/6 mice with bacterial lipopolysaccharide, 1 μg/g body weight, i.p. At various time points (0–48 h) after stimulation, liver tissue sections were prepared for immunohistochemistry. Confocal microscopy was used to detect the expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, intercellular adhesion molecule-1 (ICAM-1) and αv integrin. The expression patterns were quantitatively measured by histomorphometry. Under basal conditions, ICAM-1 was weakly expressed in terminal portal veins while minimal VCAM-1 and no E-selectin were detected. Following stimulation with lipopolysaccharide, VCAM-1 and E-selectin were expressed on the endothelium of terminal portal veins and on sinusoidal lining cells with significantly stronger expression in the periportal zone than midzone. VCAM-1 expression peaked at 4 h and decreased gradually by 48 h. E-selectin peaked at 2 h and disappeared by 12 h after stimulation. ICAM-1 expression showed a much stronger and more uniform expression across the acinus with the peak reached by 4 h and sustained for longer than 48 h after lipopolysaccharide administration. The αv integrin was not detected under basal conditions or after lipopolysaccharide stimulation. Expression of all these adhesion molecules (ICAM-1, VCAM-1, E-selectin and αv integrin) was induced by growth of B16F1 melanoma cells in the peritoneal cavity of the mouse. These results support the hypotheses that expression of microvascular adhesion molecules in the mouse liver is susceptible to regulation by environmental stimuli and has a zonal heterogeneity across the acinus.
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References
Rappaport AM. The microcirculatory acinar concept of normal and pathologic hepatic structure. Beitr Pathol 1976; 157: 215–243.
Sasse D, Spornitz UM, Maly IP. Liver architecture. Enzyme 1992; 46: 8–32.
Jungermann K, Katz N. Functional specialization of different hepatocyte populations. Physiol Rev 1989; 69: 708–764.
Bouwens L, De Bleser P, Vanderkerken K, Geerts B, Wisse E. Liver cell heterogeneity: functions of non-parenchymal cells. Enzyme 1992; 46: 155–168.
Vidal-Vanaclocha F, Rocha M, Asumendi A, Barbera-Guillem E. Isolation and enrichment of two sublobular compartment-specific endothelial cell subpopulations from liver sinusoids. Hepatology 1993; 18: 328–339.
Mendoza L, Olaso E, Anasagasti MJ, Fuentes AM, Vidal-Vanaclocha F. Mannose receptor-mediated endothelial cell activation contributes to B16 melanoma cell adhesion and metastasis in liver. J Cell Physiol 1998; 174: 322–330.
Brodt P, Fallavollita L, Bresalier RS, Meterissian S, Norton CR, Wolitzky BA. Liver endothelial E-selectin mediates carcinoma cell adhesion and promotes liver metastasis. Int J Cancer 1997; 71: 612–619.
Vidal-Vanaclocha F, Alvarez A, Asumendi A, Urcelay B, Tonino P, Dinarello CA. Interleukin-1 (IL-1)-dependent melanoma hepatic metastasis in vivo; increased endothelial adherence by IL-1–induced mannose receptors and growth factor production in vitro. J Natl Cancer Inst 1996; 88: 198–205.
Scherbarth S, Orr FW. Intravital videomicroscopic evidence for regulation of metastasis by the hepatic microvasculature: effects of interleukin-1aonmetastasis and the location of B16F1 melanoma cell arrest. Cancer Res 1997; 57: 4105–4110.
Pober JS, Jr Gimbrone MA, Lapierre LA, Mendrick, DL, Fiers W, Rothlein R, Springer TA. Overlapping patterns of activation of human endothelial cells by interleukin-1, tumor necrosis factor, and immune interferon. J Immunol 1986; 137: 1893–1896.
Fries JW, Williams AJ, Atkins RC, Newman W, Lipscomb MF, Collins T. Expression of VCAM-1 and E-selectin in an in vivo model of endothelial activation. Am J Pathol 1993; 143: 725–737.
Wan W, Wetmore L, Sorensen CM, Greenberg AH, Nance DM. Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain. Brain Res Bull 1994; 34: 7–14.
Meltzer JC, Grimm PC, Greenberg AH, Nance DM. Enhanced immunohistochemical detection of autonomic nerve fibers, cytokines and inducible nitric oxide synthase by light and fluorescent microscopy in rat spleen. J Histochem Cytochem 1997; 45: 599–610.
Lafrenie RM, Podor TJ, Buchanan MR, Orr FW. Upregulated biosynthesis and expression of endothelial cell vitronectin receptor enhances cancer cell adhesion. Cancer Res 1992; 52: 2202–2208.
Nip J, Brodt P. The role of the integrin vitronectin receptor, avß 3 in melanoma metastasis. Cancer Metastasis Rev 1995; 14: 241–252.
Chambers AF, MacDonald IC, Schmidt EE, Koop S, Morris VL, Khokha R, Groom AC. Steps in tumor metastasis: new concepts from intravital videomicroscopy. Cancer Metastasis Rev 1995; 14: 279–301.
Jungermann K. Zonal liver cell heterogeneity. Enzyme 1992; 46: 5–7.
Van Bossuyt H, Bouwens L, Wisse E. Isolation, purification and culture of sinusoidal liver cells. In: Bioulac-Sage P, Balabaud C (eds) Sinusoids in Human Liver: Health and Disease. Rijswijk: Kupffer Cell Foundation 1988; 1–16.
Bouwens L, Baekeland M, De Zanger R, Wisse E. Quantitation, tissue distribution and proliferation kinetics of Kupffer cells in normal rat liver. Hepatology 1986; 6: 718–722.
Sleyster EC, Knock DL. Relation between localization and function of rat liver Kupffer cells. Lab Invest 1982; 47: 484–490.
Bouwens L, Jacobs R, Remels L, Wisse E. Natural cytotoxicity of rat hepatic natural killer cells and macrophages against a syngeneic colon adenocarcinoma. Cancer Immunol Immunother 1988; 27: 137–141.
Vanderkerken K, Bouwens L, Wisse E. Characterization of a phenotypically and functionally distinct subset of large granular lymphocytes (Pit cells) in rat liver sinusoids. Hepatology 1990; 12: 70–75.
Zou Z, Ekataksin W, Wake K. Zonal and regional differences identified from precision mapping of vitamin A-storing lipid droplets of the hepatic stellate cells in pig liver: a novel concept of addressing the intralobular area of heterogeneity. Hepatology 1992; 27: 1098–1108.
Reid LM, Fiorino AS, Sigal SH, Brill S, Holst PA. Extracellular matrix gradients in the space of Disse: Relevance to liver biology. Hepatology 1992; 15: 1198–1203.
Wisse E, De Zanger RB, Charels K, Van Der Smissen P, McCuskey RS. The liver sieve: Considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology 1985; 5: 683–692.
Barbera-Guillem E, Rocha M, Alvarez A, Vidal-Vanaclocha F. Differences in the lectin-binding patterns of the periportal and perivenous endothelial domains in the liver sinusoids. Hepatology. 1991; 14: 131–139.
Asumendi A, Alvarez A, Martinez I, Smedsod B, Vidal-Vanaclocha F. Hepatic sinusoidal endothelium heterogeneity with respect to mannose receptor activity is interleukin-1 dependent. Hepatology 1996; 23: 1521–1529.
Scoazec JY, Racine L, Couvelard A, Flejou JF, Feldmann G. Endothelial cell heterogeneity in the normal human liver acinus: in situ immunohistochemical demonstration. Liver 1994; 14: 113–123.
Volpes R, Van-Den-Oord JJ, Desmet VJ. Vascular adhesion molecules in acute and chronic liver inflammation. Hepatology 1992; 15: 269–275.
Neumann B, Machleidt T, Lifka A, Pfeffer K, Vestweber D, Mak TW, Holzmann B Kronke M. Crucial role of 55–kilodalton TNF receptor in TNF-induced adhesion molecule expression and leukocyte organ infiltration. J Immunol 1996; 156: 1587–1593.
Lopez S, Borras D, Juan-Salles C, Prats N, Domingo M, Marco AJ. Immunohistochemical detection of adhesion molecules intercellular adhesion molecule-1 and E-selectin in formalin-fixed, paraffinembedded mouse tissues. Lab Invest 1997; 77: 543–544.
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Wang, H.H., Nance, D.M. & Orr, F.W. Murine hepatic microvascular adhesion molecule expression is inducible and has a zonal distribution. Clin Exp Metastasis 17, 149–155 (1999). https://doi.org/10.1023/A:1006685628224
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DOI: https://doi.org/10.1023/A:1006685628224