SUMMARY AT A GLANCE: Secretory leukocyte proteinase inhibitor (SLPI) is a major anti-elastase barrier at the epithelial surfaces of upper respiratory tract. Our findings indicate clear up-regulation of SLPI in response to endotoxin in nasal secretions. In addition, SLPI shows dose-dependent anti-apoptotic and chemotactic effects on primary human neutrophils. ABSTRACT: Background and objective: The Secretory Leukocyte Protease Inhibitor (SLPI) is a major anti-elastase barrier at the epithelial surfaces of upper respiratory tract. In addition to its anti-protease activity, SLPI has been shown to express anti-bacterial, anti-viral and anti-inflammatory properties. Methods: We measured SLPI concentration in nasal lavage fluid of healthy volunteers after challenge with endotoxin (LPS) and evaluated SLPI effects in vitro on neutrophil chemotaxis, adhesion, cytokine (IL-8) release and apoptosis. Results: SLPI concentration in nasal lavage (n = 9) 2, 6 and 24 hrs after the challenge with LPS (25 µg) increased from 32% to 238% compared to baseline (226 ± 71 ng/ml). In vitro, SLPI (20 to 80µg/ml) induced neutrophil chemotaxis (6-fold, p < 0.001) and decreased neutrophil apoptosis by 73% (p = 0.006), relative to controls. However, SLPI had no affect on IL-8 release or neutrophil adhesion to fibronectin. SLPI-positive immunoreactivity was co-localised with neutrophils in lung specimens from patients with chronic obstructive pulmonary disease. Conclusions: Our findings indicate up-regulation of SLPI in response to LPS in nasal secretions and show anti-apoptotic effects of SLPI in primary human neutrophils suggesting a new role of SLPI during neutrophilic inflammation.
- Immunologi inom det medicinska området
- Reumatologi och inflammation