Interleukin-8 induces neutrophil accumulation but not protease secretion in the canine trachea.
The neutrophil enzyme elastase is a potent secretagogue of airway secretory cells, and elastase is present in high concentrations in sputum of patients with hypersecretion (e.g., cystic fibrosis, bronchiectasis). Interleukin-8 (IL-8), a recently discovered cytokine with potent neutrophil chemotactic properties in vitro, is also found in the sputum of these patients. We used an isolated tracheal segment in dogs in vivo to study the effect of IL-8 in causing neutrophil accumulation, elastase release, and secretion (by measuring lysozyme concentrations) in the luminal superfusate. IL-8 caused a potent time-dependent neutrophil accumulation at between 3 and 6 h. The effect was significant at 10(-9) and maximum at 10(-8) M. No increase in free elastase, cathepsin G, or lysozyme was detected in the superfusate. Thus, in contrast to previous studies showing that ragweed antigen causes the accumulation of neutrophil elastase which in turn causes lysozyme secretion, IL-8 causes neutrophil accumulation without granule secretion (or subsequent secretagogue activity). The findings were confirmed with dog and human neutrophils in vitro.
Jorens
P G
PG
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Richman-Eisenstat
J B
JB
Housset
B P
BP
Graf
P D
PD
Ueki
I F
IF
Olesch
J
J
Nadel
J A
JA
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004285:Dogs; D010450:Endopeptidases / Q000378:metabolism*; D016209:Interleukin-8 / Q000494:pharmacology*; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D009994:Osmolar Concentration; D010196:Pancreatic Elastase / Q000378:metabolism; D010477:Perfusion; D014132:Trachea / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D016209:Interleukin-8; D009113:Muramidase; D010450:Endopeptidases; D010196:Pancreatic Elastase