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Am J Physiol Lung Cell Mol Physiol 273: L618-L625, 1997;
1040-0605/97 $5.00
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AJP - Lung Cellular and Molecular Physiology, Vol 273, Issue 3 618-L625, Copyright © 1997 by American Physiological Society

ARTICLES

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

K. Soejima, S. Fujishima, H. Nakamura, Y. Waki, M. Nakamura, H. Matsubara, S. Tasaka, K. Sayama, A. Ishizaka and M. Kanazawa
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.

We examined the expression of interleukin (IL)-8 receptors (Rs), type A (IL-8-RA) and type B (IL-8-RB), 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-1 beta 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-1 beta. Staurosporine reduced the downmodulation by low-level IL-8 plus LTB4 or IL-1 beta but not by high-level IL-8 alone. We speculate that pulmonary IL-8-RA and IL-8-RB may have been downmodulated by the combined effect of local chemoattractants through, in part, a protein kinase C-dependent mechanism.


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