Active Oxidants Mediate IFN-α-Induced Microvascular Alterations in Rat Mesentery

Hajime Higuchi, Iwao Kurose, Dai Fukumura, Han Jing Yan, Hidetsugu Saito, Soichiro Miura, Ryota Hokari, Naoyuki Watanabe, Shigeyuki Zeki, Masashi Yoshida, Masaki Kitajima, D. Neil Granger, Hiromasa Ishii

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11 Citations (Scopus)

Abstract

The present study was designed to investigate the influences of IFN-α on the microcirculatory hemodynamics. The mesenteric microcirculation of male Wistar rats was observed through an intravital fluorescence microscopic system. The leukocyte behavior, RBC velocity, and albumin leakage were monitored simultaneously before and after a continuous infusion of IFN-α. In other rats, the oxidant-sensitive fluorescence probe dihydrorhodamine-123 (DHR) fluorescence was observed in the same set up. Administration of IFN-α increased the number of adherent and emigrated leukocytes and decreased the RBC velocity in mesenteric venules. Oxidative stress indicated by DHR fluorescence was exacerbated in microvessels of IFN-α-treated rats. Following the leukocyte recruitment and oxidative stress, an exaggerated albumin leakage was observed. Thrombus formation in venules and hemorrhage along venules were frequently observed in rats treated with IFN-α. N,N′-dimethylthiourea, a scavenger of hydrogen peroxide and a hydroxyl radical, largely prevented these microvascular responses. Pretreatment of rats with mAb directed against either CD18 or ICAM-1 also attenuated the IFN-α-induced microvascular alterations. It is concluded, therefore, that a high concentration of IFN-α stimulates CD18/ICAM-1-dependent adhesive interactions with endothelial cells and oxidant production of leukocytes, which leads to microcirculatory derangements characterized by decreased barrier function and reduced anticoagulant activity of venular endothelial cells.

Original languageEnglish
Pages (from-to)4893-4900
Number of pages8
JournalJournal of Immunology
Volume158
Issue number10
Publication statusPublished - 1997 May 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Higuchi, H., Kurose, I., Fukumura, D., Yan, H. J., Saito, H., Miura, S., Hokari, R., Watanabe, N., Zeki, S., Yoshida, M., Kitajima, M., Granger, D. N., & Ishii, H. (1997). Active Oxidants Mediate IFN-α-Induced Microvascular Alterations in Rat Mesentery. Journal of Immunology, 158(10), 4893-4900.