Molecular, cellular and functional characterizations of a novel ICAM-like molecule of the immunoglobulin superfamily from Leishmania mexicana amazonensis

A molecule with two immunoglobulin (Ig) domains cloned from Leishmania mexi cana amazonensis was characterized to have a sequence homology to the Ip do mains of an ICAM-like molecule telencephalin. cloned from the brain of mamm als, as well as to the variable domains of human immunoglobulin lambda ligh t chain. The molecule therefore appears to be an ICAM-like molecule as well as a member of the immunoglobulin superfamily. We thus named it ICAM-L for Leishmania ICAM. The gene was coamplified with the ribonucleotide reductas e M-3 subunit gene responsible for hydroxyurea resistance from hydroxyurea (Hu)-resistant Leishmania variants. As expected, an increase of the ICAM-L protein as well as an increase of the specific ICAM-L transcript of 2.1 kb was detected in the Hu-resistant variants with increasing doses of the drug used for resistance selection. Structurally. ICAM-L is more similar to the secretory adhesive molecules, such as 1Bgp and the link protein of the imm unoglobulin superfamily. in that it lacks a transmembrane region and a GPI anchor sequence. Although ICAM-L was mainly localized in the nucleus of the parasite by confocal microscopy. however, detailed studies by electron mic roscopy and FAGS analysis: indicated that the protein was also localized on the surface of the parasite. The surface localization of the protein was f urthered strengthened by the: observations that anti-ICAM-L or ICAM-L itsel f can significantly block the binding of the parasite to macrophages. The b locking of the attachment of parasite to macrophages may indicate that ICAM -L functions as an intercellular adhesive molecule. (C) 2001 Elsevier Scien ce B.V. All rights reserved.