Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis

Zhongbin Bai, Linjun Cai, Eiji Umemoto, Akira Takeda, Kazuo Tohya, Yutaka Komai, Punniyakoti Thanikachalam Veeraveedu, Erina Hata, Yuki Sugiura, Akiko Kubo, Makoto Suematsu, Haruko Hayasaka, Shinichi Okudaira, Junken Aoki, Toshiyuki Tanaka, Harald M H G Albers, Huib Ovaa, Masayuki Miyasaka

Research output: Contribution to journalArticle

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Abstract

Lymphocyte extravasation from the high endothelial venules (HEVs) of lymph nodes is crucial for the maintenance of immune homeostasis, but its molecular mechanism remains largely unknown. In this article, we report that lymphocyte transmigration across the basal lamina of the HEVs is regulated, at least in part, by autotaxin (ATX) and its end-product, lysophosphatidic acid (LPA). ATX is an HEV-associated ectoenzyme that produces LPA from lysophosphatidylcholine (LPC), which is abundant in the systemic circulation. In agreement with selective expression of ATX in HEVs, LPA was constitutively and specifically detected on HEVs. In vivo, inhibition of ATX impaired the lymphocyte extravasation from HEVs, inducing lymphocyte accumulation within the endothelial cells (ECs) and sub-EC compartment; this impairment was abrogated by LPA. In vitro, both LPA and LPC induced a marked increase in the motility of HEV ECs; LPC's effect was abrogated by ATX inhibition, whereas LPA's effect was abrogated by ATX/LPA receptor inhibition. In an in vitro transmigration assay, ATX inhibition impaired the release of lymphocytes that had migrated underneath HEV ECs, and these defects were abrogated by LPA. This effect of LPA was dependent on myosin II activity in the HEV ECs. Collectively, these results strongly suggest that HEV-associated ATX generates LPA locally; LPA, in turn, acts on HEV ECs to increase their motility, promoting dynamic lymphocyte-HEV interactions and subsequent lymphocyte transmigration across the basal lamina of HEVs at steady state.

Original languageEnglish
Pages (from-to)2036-2048
Number of pages13
JournalJournal of Immunology
Volume190
Issue number5
DOIs
Publication statusPublished - 2013 Mar 1

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Venules
Basement Membrane
Lymphocytes
Endothelial Cells
Lysophosphatidylcholines
lysophosphatidic acid
Lysophosphatidic Acid Receptors
Myosin Type II
Homeostasis

ASJC Scopus subject areas

  • Immunology

Cite this

Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis. / Bai, Zhongbin; Cai, Linjun; Umemoto, Eiji; Takeda, Akira; Tohya, Kazuo; Komai, Yutaka; Veeraveedu, Punniyakoti Thanikachalam; Hata, Erina; Sugiura, Yuki; Kubo, Akiko; Suematsu, Makoto; Hayasaka, Haruko; Okudaira, Shinichi; Aoki, Junken; Tanaka, Toshiyuki; Albers, Harald M H G; Ovaa, Huib; Miyasaka, Masayuki.

In: Journal of Immunology, Vol. 190, No. 5, 01.03.2013, p. 2036-2048.

Research output: Contribution to journalArticle

Bai, Z, Cai, L, Umemoto, E, Takeda, A, Tohya, K, Komai, Y, Veeraveedu, PT, Hata, E, Sugiura, Y, Kubo, A, Suematsu, M, Hayasaka, H, Okudaira, S, Aoki, J, Tanaka, T, Albers, HMHG, Ovaa, H & Miyasaka, M 2013, 'Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis', Journal of Immunology, vol. 190, no. 5, pp. 2036-2048. https://doi.org/10.4049/jimmunol.1202025
Bai, Zhongbin ; Cai, Linjun ; Umemoto, Eiji ; Takeda, Akira ; Tohya, Kazuo ; Komai, Yutaka ; Veeraveedu, Punniyakoti Thanikachalam ; Hata, Erina ; Sugiura, Yuki ; Kubo, Akiko ; Suematsu, Makoto ; Hayasaka, Haruko ; Okudaira, Shinichi ; Aoki, Junken ; Tanaka, Toshiyuki ; Albers, Harald M H G ; Ovaa, Huib ; Miyasaka, Masayuki. / Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis. In: Journal of Immunology. 2013 ; Vol. 190, No. 5. pp. 2036-2048.
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AU - Bai, Zhongbin

AU - Cai, Linjun

AU - Umemoto, Eiji

AU - Takeda, Akira

AU - Tohya, Kazuo

AU - Komai, Yutaka

AU - Veeraveedu, Punniyakoti Thanikachalam

AU - Hata, Erina

AU - Sugiura, Yuki

AU - Kubo, Akiko

AU - Suematsu, Makoto

AU - Hayasaka, Haruko

AU - Okudaira, Shinichi

AU - Aoki, Junken

AU - Tanaka, Toshiyuki

AU - Albers, Harald M H G

AU - Ovaa, Huib

AU - Miyasaka, Masayuki

PY - 2013/3/1

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N2 - Lymphocyte extravasation from the high endothelial venules (HEVs) of lymph nodes is crucial for the maintenance of immune homeostasis, but its molecular mechanism remains largely unknown. In this article, we report that lymphocyte transmigration across the basal lamina of the HEVs is regulated, at least in part, by autotaxin (ATX) and its end-product, lysophosphatidic acid (LPA). ATX is an HEV-associated ectoenzyme that produces LPA from lysophosphatidylcholine (LPC), which is abundant in the systemic circulation. In agreement with selective expression of ATX in HEVs, LPA was constitutively and specifically detected on HEVs. In vivo, inhibition of ATX impaired the lymphocyte extravasation from HEVs, inducing lymphocyte accumulation within the endothelial cells (ECs) and sub-EC compartment; this impairment was abrogated by LPA. In vitro, both LPA and LPC induced a marked increase in the motility of HEV ECs; LPC's effect was abrogated by ATX inhibition, whereas LPA's effect was abrogated by ATX/LPA receptor inhibition. In an in vitro transmigration assay, ATX inhibition impaired the release of lymphocytes that had migrated underneath HEV ECs, and these defects were abrogated by LPA. This effect of LPA was dependent on myosin II activity in the HEV ECs. Collectively, these results strongly suggest that HEV-associated ATX generates LPA locally; LPA, in turn, acts on HEV ECs to increase their motility, promoting dynamic lymphocyte-HEV interactions and subsequent lymphocyte transmigration across the basal lamina of HEVs at steady state.

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