Role of recruited neutrophils in interleukin-8 production in dog trachea after stimulation with Pseudomonas in vivo.

Abstract

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.

Phenazine-1-carboxylic acid, a secondary metabolite ofPseudomonas aeruginosa, alters expression of immunomodulatory proteins by human airway epithelial cells

“…Previous studies demonstrate that SMW factors from P. aeruginosa increase IL-8 release in vitro (10,22,24) as well as IL-8 release and neutrophil influx in vivo (16). Two of the factors that increase IL-8, pyocyanin, and 1-HP have been purified, and their biological effects have been studied.…”

Impairment of Endotoxin-Induced Macrophage Inflammatory Protein 2 Gene Expression in Alveolar Macrophages in Streptozotocin-Induced Diabetes in Mice

“…Among these, IL-8 has been recently recognized as an important neutrophil chemotactic and activating peptide (8,17,30). The effect of diabetes on AMs is not well characterized, and studies of the function of primary pulmonary defense cells obtained from BAL fluid from diabetic patients are limited.…”

“…Recruitment and activation of inflammatory cells at the site of infection is closely related to a family of chemotactic cytokines (17,30). Interleukin-8 (IL-8) appears to be a key C-X-C chemokine involved in neutrophil recruitment in a number of inflammatory conditions such as pneumonia (8). Whether IL-8 production and neutrophil recruitment are suppressed in diabetic patients with pneumonia is not yet clear.…”

Inflammatory Mediators in Chronic Obstructive Pulmonary Disease

“…Bacteria and bacterial products such as lipopolysaccharide can induce IL-8 expression, probably as a result of initial TNFα production [70,71]. TNFα may be important in inducing the expression of MIP-2 and MCP-1, and in connective tissue breakdown following cigarette smoke exposure [72].…”