Intercellular adhesion molecule 1 is the major adhesion molecule expressed during schistosome granuloma formation.
Endothelial cell adhesion molecules play a key role in inflammation by initiating leukocyte trafficking. One of the most complex inflammatory responses is the formation of a cellular granuloma. Expression of adhesion molecules during granuloma formation was investigated by using the murine host reaction to schistosome parasite eggs deposited in the liver as a model. By both immunohistochemistry and lymphocyte adhesion assays, the predominant interaction identified was between intercellular adhesion molecule 1 (ICAM-1) and its cognate integrin, leukocyte functional antigen 1 (LFA-1). ICAM-1 expression on sinusoidal endothelium was induced when eggs were first deposited in the liver, peaked in parallel with granuloma size, and was downregulated with modulation of the granuloma. Polyacrylamide beads coated with soluble parasite egg antigens could induce ICAM-1 expression on endothelial cells in vitro only in the presence of tumor necrosis factor alpha, a cytokine previously shown to be key to granuloma formation. A role for ICAM-1 in recruiting lymphocytes to the hepatic granuloma was also supported by the observation that lymphocytes preincubated with anti-LFA-1 antibody did not bind to granulomas in tissue sections. While ICAM-1 is the predominant adhesion molecule in schistosome egg granuloma formation in wild-type mice, when the ICAM-1 gene is knocked out, vascular cell adhesion molecule 1 is upregulated and granuloma formation is preserved.
Department of Pathology, University of California at San Francisco, USA.
D M
DM
Ritter
J H
JH
McKerrow
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004727:Endothelium / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D010063:Ovum / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000947:Antigens, Helminth; D016169:Lymphocyte Function-Associated Antigen-1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1