Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells

Y Tanaka, S Mine, C G Figdor, A Wake, H Hirano, J Tsukada, M Aso, K Fujii, K Saito, Y van Kooyk, S Eto

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Adult T-cell leukemia (ATL) is characterized by massive infiltration of circulating ATL cells into a variety of tissues, a finding often associated with poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium, and integrins are tightly regulated by several stimuli, such as inflammatory chemokines. However, the exact mechanisms that enhance adherence of leukemic cells to the endothelium and infiltration into tissues remain to be fully understood. We investigated the mechanisms of extravasation of leukemic cells using ATL cells and report the following novel features of endogenous chemokine-induced adhesion of ATL cells to the endothelium. ATL cells spontaneously adhered to endothelial cells without exogenous stimulation. Integrin leukocyte function-associated antigen-1 (LFA-1) on ATL cells was spontaneously activated. ATL cells produced high amounts of chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Adhesion of ATL cells to endothelial cells and the expression of activated form of LFA-1 were reduced by pretreatment with pertussis toxin, wortmannin, or anti-MIP-1alpha and MIP-1beta antibodies or transfection with antisense of MIP-1alpha or MIP-1beta. Spontaneous polymerization of cytoskeletal F-actin was observed in ATL cells, which was also inhibited by pertussis toxin and wortmannin. We propose that ATL cells adhere to endothelial cells through an adhesion cascade similar to normal leukocytes and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent activation of phosphoinositide 3-kinases in an autocrine manner. These events result in a strong adhesion of ATL cells to the endothelium and spontaneous transendothelial migration.

Original languageEnglish
Pages (from-to)3909-19
Number of pages11
JournalBlood
Volume91
Issue number10
Publication statusPublished - 15 May 1998

Cite this

Tanaka, Y., Mine, S., Figdor, C. G., Wake, A., Hirano, H., Tsukada, J., ... Eto, S. (1998). Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells. Blood, 91(10), 3909-19.
Tanaka, Y ; Mine, S ; Figdor, C G ; Wake, A ; Hirano, H ; Tsukada, J ; Aso, M ; Fujii, K ; Saito, K ; van Kooyk, Y ; Eto, S. / Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells. In: Blood. 1998 ; Vol. 91, No. 10. pp. 3909-19.
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abstract = "Adult T-cell leukemia (ATL) is characterized by massive infiltration of circulating ATL cells into a variety of tissues, a finding often associated with poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium, and integrins are tightly regulated by several stimuli, such as inflammatory chemokines. However, the exact mechanisms that enhance adherence of leukemic cells to the endothelium and infiltration into tissues remain to be fully understood. We investigated the mechanisms of extravasation of leukemic cells using ATL cells and report the following novel features of endogenous chemokine-induced adhesion of ATL cells to the endothelium. ATL cells spontaneously adhered to endothelial cells without exogenous stimulation. Integrin leukocyte function-associated antigen-1 (LFA-1) on ATL cells was spontaneously activated. ATL cells produced high amounts of chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Adhesion of ATL cells to endothelial cells and the expression of activated form of LFA-1 were reduced by pretreatment with pertussis toxin, wortmannin, or anti-MIP-1alpha and MIP-1beta antibodies or transfection with antisense of MIP-1alpha or MIP-1beta. Spontaneous polymerization of cytoskeletal F-actin was observed in ATL cells, which was also inhibited by pertussis toxin and wortmannin. We propose that ATL cells adhere to endothelial cells through an adhesion cascade similar to normal leukocytes and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent activation of phosphoinositide 3-kinases in an autocrine manner. These events result in a strong adhesion of ATL cells to the endothelium and spontaneous transendothelial migration.",
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author = "Y Tanaka and S Mine and Figdor, {C G} and A Wake and H Hirano and J Tsukada and M Aso and K Fujii and K Saito and {van Kooyk}, Y and S Eto",
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Tanaka, Y, Mine, S, Figdor, CG, Wake, A, Hirano, H, Tsukada, J, Aso, M, Fujii, K, Saito, K, van Kooyk, Y & Eto, S 1998, 'Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells' Blood, vol. 91, no. 10, pp. 3909-19.

Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells. / Tanaka, Y; Mine, S; Figdor, C G; Wake, A; Hirano, H; Tsukada, J; Aso, M; Fujii, K; Saito, K; van Kooyk, Y; Eto, S.

In: Blood, Vol. 91, No. 10, 15.05.1998, p. 3909-19.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells

AU - Tanaka, Y

AU - Mine, S

AU - Figdor, C G

AU - Wake, A

AU - Hirano, H

AU - Tsukada, J

AU - Aso, M

AU - Fujii, K

AU - Saito, K

AU - van Kooyk, Y

AU - Eto, S

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N2 - Adult T-cell leukemia (ATL) is characterized by massive infiltration of circulating ATL cells into a variety of tissues, a finding often associated with poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium, and integrins are tightly regulated by several stimuli, such as inflammatory chemokines. However, the exact mechanisms that enhance adherence of leukemic cells to the endothelium and infiltration into tissues remain to be fully understood. We investigated the mechanisms of extravasation of leukemic cells using ATL cells and report the following novel features of endogenous chemokine-induced adhesion of ATL cells to the endothelium. ATL cells spontaneously adhered to endothelial cells without exogenous stimulation. Integrin leukocyte function-associated antigen-1 (LFA-1) on ATL cells was spontaneously activated. ATL cells produced high amounts of chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Adhesion of ATL cells to endothelial cells and the expression of activated form of LFA-1 were reduced by pretreatment with pertussis toxin, wortmannin, or anti-MIP-1alpha and MIP-1beta antibodies or transfection with antisense of MIP-1alpha or MIP-1beta. Spontaneous polymerization of cytoskeletal F-actin was observed in ATL cells, which was also inhibited by pertussis toxin and wortmannin. We propose that ATL cells adhere to endothelial cells through an adhesion cascade similar to normal leukocytes and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent activation of phosphoinositide 3-kinases in an autocrine manner. These events result in a strong adhesion of ATL cells to the endothelium and spontaneous transendothelial migration.

AB - Adult T-cell leukemia (ATL) is characterized by massive infiltration of circulating ATL cells into a variety of tissues, a finding often associated with poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium, and integrins are tightly regulated by several stimuli, such as inflammatory chemokines. However, the exact mechanisms that enhance adherence of leukemic cells to the endothelium and infiltration into tissues remain to be fully understood. We investigated the mechanisms of extravasation of leukemic cells using ATL cells and report the following novel features of endogenous chemokine-induced adhesion of ATL cells to the endothelium. ATL cells spontaneously adhered to endothelial cells without exogenous stimulation. Integrin leukocyte function-associated antigen-1 (LFA-1) on ATL cells was spontaneously activated. ATL cells produced high amounts of chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Adhesion of ATL cells to endothelial cells and the expression of activated form of LFA-1 were reduced by pretreatment with pertussis toxin, wortmannin, or anti-MIP-1alpha and MIP-1beta antibodies or transfection with antisense of MIP-1alpha or MIP-1beta. Spontaneous polymerization of cytoskeletal F-actin was observed in ATL cells, which was also inhibited by pertussis toxin and wortmannin. We propose that ATL cells adhere to endothelial cells through an adhesion cascade similar to normal leukocytes and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent activation of phosphoinositide 3-kinases in an autocrine manner. These events result in a strong adhesion of ATL cells to the endothelium and spontaneous transendothelial migration.

KW - 3-Phosphoinositide-Dependent Protein Kinases

KW - Actins/metabolism

KW - Adult

KW - Androstadienes/pharmacology

KW - Antibodies, Monoclonal/pharmacology

KW - Cell Adhesion

KW - Cells, Cultured

KW - Chemokine CCL3

KW - Chemokine CCL4

KW - Chemotaxis, Leukocyte/drug effects

KW - DNA, Antisense/pharmacology

KW - Endothelium, Vascular/cytology

KW - Enzyme Activation

KW - GTP-Binding Proteins/physiology

KW - Humans

KW - Leukemia-Lymphoma, Adult T-Cell/immunology

KW - Lymphocyte Activation

KW - Lymphocyte Function-Associated Antigen-1/metabolism

KW - Macrophage Inflammatory Proteins/biosynthesis

KW - Neoplastic Cells, Circulating/drug effects

KW - Neoplastic Stem Cells/drug effects

KW - Pertussis Toxin

KW - Protein-Serine-Threonine Kinases/metabolism

KW - Signal Transduction/physiology

KW - T-Lymphocytes/drug effects

KW - Umbilical Veins

KW - Virulence Factors, Bordetella/pharmacology

M3 - Article

VL - 91

SP - 3909

EP - 3919

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -

Tanaka Y, Mine S, Figdor CG, Wake A, Hirano H, Tsukada J et al. Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells. Blood. 1998 May 15;91(10):3909-19.