Abstract
Introduction: PolyI:C is a synthetic dsRNA that triggers an innate immune response through the activation of TLR3 and RNA helicases. Our aim was to dissect the mechanism driving polyI:C-induced airway neutrophilia.
Methods: Male, BALB/c mice were intranasally administered polyI:C (30 mg/animal) or saline under isofluorane. Bronchoalveolar lavage fluid (BALF) was collected 2-168h later (n=8). BALF cells were counted and inflammatory mediators were measured in BALF supernatants by ELISA. The efficacy of a CXCR2 antagonist, SCH563750 (3-30 mg/kg) or its vehicle (2% Klucel, 0.1% Tween 80 in water), was assessed by administering p.o. 1h prior to polyI:C challenge. Airway hyper-responsiveness (AHR) and BALF inflammation were assessed 24h later.
Results: Administration of polyI:C increased several mediators in the BALF. Greatest amongst these was KC, peaking at 2h (2366±397 in polyI:C vs 8±1 control animals; P<0.01) and remaining elevated up to 72h. Neutrophil infiltration followed the increased KC levels, increasing from 6h before resolving back to baseline at 96h. Lymphocytes, predominantly CD49b+ NK cells, increased from 24h and were still elevated 168h post-challenge. SCH563750 attenuated the neutrophils in the BALF by 92% at a dose of 30 mg/kg (P<0.01). SCH563750 had no effect on BALF lymphocytes or AHR, although there was a trend towards a reversal of the latter.
Conclusion: Poly I:C administration to the airways increased chemokine levels, including KC. The influx of neutrophils was abrogated by a CXCR2 inhibitor. The lack of neutrophil infiltrate did not affect lymphocyte migration to the airways, suggesting an independent mechanism drives this response.
- © 2011 ERS