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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
A Wake, Y Tanaka, K Nakatsuka, M Misago, S Oda, I Morimoto and S Eto
First Department of Internal Medicine, University of Occupational and
Environmental Health, School of Medicine, Kitakyushu, Japan.
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.
Volume 86,
Issue 6,
pp. 2257-2267,
09/15/1995
Copyright © 1995 by The American Society of Hematology
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