Secretory leukocyte protease inhibitor inhibits neutrophil apoptosis.

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 h after the challenge with LPS (25 µg) increased from 32% to 238% compared with baseline (226 ± 71 ng/mL). In vitro, SLPI (20-80 µg/mL) induced neutrophil chemotaxis (sixfold, 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-localized with neutrophils in lung specimens from patients with COPD.

CONCLUSIONS

Our findings indicate upregulation 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.