Expression of intercellular adhesion molecule-1 and lymphocytefunction-associated antigen-1 in experimental Schistosoma mansoni infection and in synchronous periparticular hepatic granulomas in mice: immunohistochemistry, confocal laser scanning microscopy, and immunoelectron microscopy

Abstract

Adhesion molecules play an important role in inflammatory and immunological responses. We assessed the expression pattern of intercellular adhesion molecule-1 (ICAM-1) and lymphocytefunction-associated antigen-1 (LFA-1) in the livers of mice experimentally infected with Schistosoma mansoni and in synchronous hepatic granulomas induced by injection of soluble egg antigen (SEA)-coupled Sepharose beads in a mesenteric vein of mice. By immunohistochemistry, confocal laser scanning microscopy, and immunoelectron microscopy, ICAM-1 was localized on endothelial cells, sinusoidal-lining cells (Kupffer cells and sinusoidal endothelium), the hepatocyte cell membrane facing Disse's space, and inflammatory cells in the granuloma. LFA-1 was visualized on the inflammatory cells of the granuloma and on phagocytic sinusoidal-lining cells, most likely Kupffer cells. ICAM-1- and LFA-1-immunoreactive cells were present in the granuloma as early as at 3 days after injection of SEA-coupled beads and persisted with time. As granulomas became older, nonimmunoreactive granuloma cells appeared. We conclude that adhesion molecules play an important role in the genesis of the schistosomal granuloma.

Adhesion and Co-stimulatory Molecules in the Pathogenesis of Hepatic and Intestinal Schistosomiasis Mansoni

“…The adhesion molecules ICAM-1 and VCAM-1 are both expressed in S. mansoni egg granulomas (Rathore et al 1996, Jacobs et al 1997b, an observation consistent with the data of Lukacs et al (1994), who could demonstrate an increase of ICAM-1 mRNA when eggs were injected in the lungs of mice to induce granulomas. Passive immunization of mice with anti-ICAM-1 monoclonal antibodies resulted in attenuation of granuloma development and reduced the proliferative response of spleen lymphocytes towards soluble egg antigens.…”

“…We could not detect hepatocyte ICAM-1 reactivity by immunohistochemistry nor by confocal microscopy. Using immunogold electron microscopy we were only able to demonstrate the presence of ICAM-1 on the microvilli of the hepatocyte cell membrane facing Disse's space (Jacobs et al 1997b). Noteworthy is that all of these pathologies -except schistosomiasis -are the result of an immune aggression against the hepatocyte.…”

“…Blockade of ICAM-1, LFA-1, and VLA-4 by monoclonal antibodies markedly inhibits spleen and granuloma cell interleukin (IL)2 and IL4 production -both cytokines being crucial for the initial events of schistosomal granuloma formation (Lukacs & Boros 1993, Wynn et al 1993) -as well as lymphoproliferative responses, both in the acute and chronic infection (Langley & Boros 1995). As infection ages, granulomas appear with a non-homogenous ICAM-1/LFA-1 staining pattern, in contrast to homogenous staining granulomas during acute infection (Jacobs et al 1997b). Whether this is due to the appearance of new cellular granuloma constituents that lack ICAM-1 or LFA-1 expression or that cellular expression is switched off in aging granulomas of previously immunoreactive cells is unclear, but since Langley and Boros (1995) did not observe apparent differences in the levels of expression of ICAM-1 and LFA-1 between acute-and chronic-infection granuloma derived cells, the appearance of new non-ICAM-1/LFA-1 immunoreactive cells in the granuloma co-existing with resident immunoreactive granuloma cells is most likely.…”

“…However, whereas ICAM-1 is constitutively expressed in normal liver tissue, VCAM-1 is not (Rathore et al 1996); VCAM-1 is dramatically induced with the onset of the hepatic egg deposition. Strong up-regulation of ICAM-1, its ligand molecule LFA-1, and the b integrin VLA-4, but not VLA-6 are seen in schistosome granulomas (Langley & Boros 1995, Jacobs et al 1997b. Interaction between ICAM-1 and LFA-1 appears to be the predominant interaction in schistosome egg granuloma formation, but when the ICAM-1 gene is knocked-out, up-regulation of VCAM-1 is seen and granuloma formation is preserved (Ritter & McKerrow 1996).…”

Experimental models of Schistosoma mansoni infection

“…Adhesion molecules such as ICAM-1 are presumably important for circulating cells to reach the site of the granuloma (Langley & Boros 1995, Jacobs et al 1997b) and adhesins are upregulated in acute and chronic murine infections.…”