title: Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro.
abstract: Adult T-cell leukemia (ATL) is a human T-cell leukemia virus type I (HTLV-I)-infected lymphoproliferative disorder that shows a characteristic nodular infiltration into various tissues, hypercalcemia, and subsequent rapid increase of peripheral ATL cell number. ATL cells and HTLV-I-infected T-cell lines also make cluster formation rapidly after the non-stimulative culture. However, the mechanism of the acute proliferation of ATL cells remains to be understood. We report the following novel features of homotypic adhesion via leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) pathway that suggest a role for it in cytokine production and rapid proliferation of ATL cells: (1) ATL cells show clustering in a calcium dependent manner, even at the higher concentration; (2) ATL cells consistently and highly express ICAM-1 and an active form of LFA-1, whereas integrin expression, except for LFA-1, is rather lower compared with that of normal CD4+ T cells; (3) ATL cells make conjugate formation within 6 minutes and clustering within 48 hours, both of which are inhibited by the addition of monoclonal antibodies (MoAbs) against LFA-1 and ICAM-1; (4) spontaneous mRNA transcription and protein secretion of both interleukin-1 and parathyroid hormone-related protein are observed consistently in ATL cells, and these productions are inhibited by anti-LFA-1 and anti-ICAM-1 MoAbs but are markedly increased by cross-linking of LFA-1 and ICAM-1 by the immobilized specific MoAbs; and (5) proliferative responses of ATL cells are also inhibited by these MoAbs. We propose that ATL cells proliferate in sequential events: the homotypic and calcium-dependent adhesion through LFA-1/ICAM-1, the signal transduction through these adhesion molecules, the production of cytokines, and the proliferation.
authors.affiliation: First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Wake
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Nakatsuka
authors.forename: M
authors.initials: M
authors.lastname: Misago
authors.forename: S
authors.initials: S
authors.lastname: Oda
authors.forename: I
authors.initials: I
authors.lastname: Morimoto
authors.forename: S
authors.initials: S
authors.lastname: Eto
mesh_terms: D001862:Bone Resorption / Q000097:blood / Q000209:etiology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D015490:HTLV-I Infections / Q000473:pathology; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D018799:Intercellular Adhesion Molecule-1; D002118:Calcium