Role of recruited neutrophils in interleukin-8 production in dog trachea after stimulation with Pseudomonas in vivo.
Cell-free supernatant of Pseudomonas aeruginosa (PA) recruits neutrophils into the airways indirectly by inducing the production of chemotactic factors, including interleukin-8 (IL-8). PA products stimulate IL-8 expression selectively in surface airway epithelium, gland ducts, serous cells, and recruited neutrophils. To examine the relative contribution of neutrophils in IL-8 release in the airway lumen, we studied the effect of inhibition of neutrophil recruitment on IL-8 concentration in tracheal fluid after introduction of PA supernatant into the dog trachea in vivo. Tracheal superfusion with PA supernatant caused neutrophil recruitment and increased the IL-8 concentration in the tracheal lumen; NPC 15669 inhibited both effects. To study whether migration of neutrophils into the airway lumen per se induces their expression of IL-8, we compared effects of local introduction of IL-8 and of PA supernatant into the trachea on IL-8 expression in neutrophils recruited into the trachea. PA supernatant, but not exogenous IL-8 alone, induced IL-8 mRNA expression in neutrophils recruited into the trachea. To determine what product(s) of PA stimulate IL-8 expression in neutrophils, we examined neutrophils isolated from peripheral blood. PA supernatant induced IL-8 production in neutrophils, an effect reproduced by PA lipopolysaccharide and inhibited by polymyxin B. These results suggest that neutrophils recruited into the airway lumen play a major role in local IL-8 production in airways in response to bacteria such as PA, depending on the presence of stimuli such as lipopolysaccharide.
Inoue
H
H
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
Hara
M
M
Massion
P P
PP
Grattan
K M
KM
Lausier
J A
JA
Chan
B
B
Kaneko
T
T
Isono
K
K
Jorens
P G
PG
Ueki
I F
IF
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004285:Dogs; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology*; D011112:Polymyxin B / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000235:genetics; D014132:Trachea / Q000276:immunology* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C071244:N-(9H-(2,7-dimethylfluoren-9-ylmethoxy)carbonyl)leucine; D007930:Leucine; D011112:Polymyxin B