Downmodulation of IL-8 receptors, type a and type B, on human lung neutrophils in vivo

Kenzo Soejima, Seitaro Fujishima, Hidetoshi Nakamura, Yasuhiro Waki, Morio Nakamura, Hiroaki Matsubara, Sadatomo Tasaka, Koichi Sayama, Akitoshi Ishizaka, Minoru Kanazawa

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Abstract

We examined the exnression of interleu-kin (IL)-8 receptors (Rs), type A (IL-8-RA) and type B (IL-8RB), on peripheral blood and bronchoalveolar lavage (BAL) fluid neutrophils; we also examined IL-8 and other chemoattractants in the epithelial lining fluid (ELF) of patients with chronic lower respiratory tract infection (CLI) to elucidate the in vivo regulation of IL-8Rs. Neutrophils were stained with monoclonal antibodies specific for IL-8-RA and IL-8-RB. We detected higher levels of IL-8 (81.6 ±25.4 ng/ml, mean ±SE), leukotriene (LT) B4, and IL-lβ in the ELF of the CLI patients than in their serum (P < 0.05). The expression of IL-8Rs on BAL neutrophils was significantly lower than that on peripheral blood neutrophils (P < 0.01 for both). In vitro analysis showed that low-level IL-8 (50 ng/ml) alone did not affect IL-8R expression but that it was downregulated by high-level IL-8 (500 ng/ml) alone and by low-level IL-8 in combination with LTB4 or IL-lβ. Staurosporine reduced the downmodulation by low-level IL-8 plus LTB4 or IL-lβ but not by high-level IL-8 alone. We speculate that pulmonary IL-8-RA and IL8-RB may have been downmodulated by the combined effect of local chemoattractants through, in part, a protein kinase C-dependent mechanism.

Original languageEnglish
Pages (from-to)L572-L580
JournalAmerican Journal of Physiology
Volume273
Issue number3 PART 1
Publication statusPublished - 1997 Dec 1

Keywords

  • Bronchiectasis
  • Bronchoalveolar lavage
  • Interleukin-1
  • Interleukin-8 receptors
  • Leukotriene B

ASJC Scopus subject areas

  • Physiology (medical)

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    Soejima, K., Fujishima, S., Nakamura, H., Waki, Y., Nakamura, M., Matsubara, H., Tasaka, S., Sayama, K., Ishizaka, A., & Kanazawa, M. (1997). Downmodulation of IL-8 receptors, type a and type B, on human lung neutrophils in vivo. American Journal of Physiology, 273(3 PART 1), L572-L580.