Downmodulation of IL-8 receptors, type A and type B, on human lung neutrophils in vivo.
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.
Soejima
K
K
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Fujishima
S
S
Nakamura
H
H
Waki
Y
Y
Nakamura
M
M
Matsubara
H
H
Tasaka
S
S
Sayama
K
K
Ishizaka
A
A
Kanazawa
M
M
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D012016:Reference Values; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology; D019311:Staurosporine / Q000494:pharmacology
D015703:Antigens, CD; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D019311:Staurosporine