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Activation of Human Monocytes for Enhanced Production of Interleukin 8 During Transendothelial Migration in Vitro

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Abstract

Interleukin-8 (IL-8) is a chemokine for polymorphonuclear leukocytes (PMNs) and lymphocytes, which promotes the extravasation of these inflammatory cells. In this study, we investigated IL-8 synthesis induced by the adhesive interaction between monocytes and endothelial cells during transmigration and the capacity of transmigrated monocytes to produce IL-8. Cocultured human monocytes and human umbilical vein endothelial cell (HUVEC) monolayers induced the synefgistic production of IL-8, compared with cultures of either monocytes or HUVEC monolayers alone. Coculture-induced IL-8 production almost doubled after HUVECs were stimulated with IL-1β. The induced IL-8 mRNA expression was consistent with the protein data, indicating the de novo synthesis of IL-8 by the coculture. Monoclonal antibodies (mAbs) against IL-8 inhibited the transendothelial chemotactic activity of the supernatants for PMNs by 55%. Immunohistochemistry revealed that both adherent and transmigrated monocytes and unstimulated HUVECs expressed IL-8 protein, whereas nonadherent monocytes did little. Transmigrated monocytes spontaneously secreted a 3.8-fold greater amount of IL-8 than the initial monocytes. Coculture-induced IL-8 production was inhibited about 30% by polyclonal Abs against IL-α, IL-1β, or tumor necrosis factor α, while it was not affected by mAbs against intercellular adhesion molecule 1 or vascular cell adhesion molecule 1. The results suggested that adhesive interaction during the transmigration of monocytes through HUVEC monolayers activates both cell types to produce IL-8 and that transmigrated monocytes are capable of producing ample IL-8.

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Authors and Affiliations

  1. Departments of Cardiology, Kyoritsu College of Pharmacy, Tokyo, Japan

    Masafumi Takahashi, Uichi Ikeda & Kazuyuki Shimada

  2. Section of Biochemistry, Kyoritsu College of Pharmacy, Tokyo, Japan

    Tadashi Kasahara

  3. Division of Hemopoiesis, Institute of Hematology, Jichi Medical School, Tochigi, Japan

    Sei-Ichi Kitagawa

  4. Department of Clinical and Laboratory Medicine, Tohoku University School of Medicine, Miyagi, Japan

    Yu-Ichi Takahashi

  5. Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts

    Chikao Morimoto

  6. Clinical Immunology and Rheumatology, Jichi Medical School, Tochigi, Japan

    Shogo Kano & Jun-Ichi Masuyama

Authors
  1. Masafumi Takahashi
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  2. Uichi Ikeda
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  4. Tadashi Kasahara
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  9. Jun-Ichi Masuyama
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Takahashi, M., Ikeda, U., Shimada, K. et al. Activation of Human Monocytes for Enhanced Production of Interleukin 8 During Transendothelial Migration in Vitro . J Clin Immunol 17, 53–62 (1997). https://doi.org/10.1023/A:1027388412806

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