Regulation of schistosome egg granuloma formation: host-soluble L-selectin enters tissue-trapped eggs and binds to carbohydrate antigens on surface membranes of miracidia.
Immunogenic carbohydrate epitopes are prominent in soluble egg antigens (SEA) of Schistosoma mansoni and in vivo are released through ultramicroscopic pores in the eggshell. Previously, one immunogenic carbohydrate was identified as lacto-N-fucopentaose III (LNFPIII), which contains the biologically important trisaccharide Lewis(x) (Le(x)), a weak ligand for E-, L-, and P-selectins. Selectins are involved in various inflammatory reactions, including recruitment of granulocytes. Further, L-selectin molecules are shed from leukocyte cell surfaces upon activation. These independent observations suggest that selectins may play various roles in granuloma formation and/or regulation. We tested in situ for alterations in expression of host E-, L-, or P-selectin in murine liver tissue at various times postinfection with schistosome cercariae. We found that L-selectin was expressed on cells surrounding egg granulomas, but surprisingly we also found mouse L-selectin on the surface membranes of larval miracidia within the S. mansoni ova. In contrast, neither E- nor P-selectin was found within ova. Antibodies to human or rat L-selectin or 15 other distinct mouse leukocyte surface molecules did not bind to the miracidial surface. The anti-mouse L-selectin staining of miracidia could be inhibited by wash buffer containing sulfated carbohydrates such as sulfated Le(x), heparan sulfate, fucoidan, and carrageenan. The elution studies imply that the miracidial surface and, therefore, schistosomes express sulfated glycans. The binding of soluble L-selectin to miracidia was not restricted by the genetic background of the host, as mouse L-selectin was detected on the surface of S. mansoni miracidia in livers from BALB/C, CBA/J, C57BL/6, and outbred Swiss mice. We also detected soluble mouse L-selectin binding to Schistosoma japonicum miracidia, indicating that these observations can be generalized to all schistosome infections. On the basis of these observations we hypothesize that host-soluble L-selectin traverses through pores in the eggshell and binds to target ligands on the surface membranes of miracidia; this complex formation might ultimately impede the release of soluble antigens from the eggs. The intraovum binding of mouse L-selectin to immunogenic carbohydrate antigens is a novel role for selectins, and this model may, in part, explain the down-regulation in granulomatous pathology observed following the acute phase of the disease.
Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
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D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D002241:Carbohydrates / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010063:Ovum / Q000276:immunology / Q000378:metabolism; D012547:Schistosoma / Q000276:immunology*; D012549:Schistosoma japonicum / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D019087:Selectins / Q000276:immunology / Q000378:metabolism*; D012995:Solubility
D000947:Antigens, Helminth; D000954:Antigens, Surface; D002241:Carbohydrates; D019087:Selectins