Abstract
BackgroundOzone (O3), a common air pollutant, induces exacerbation of asthma and chronic obstructive pulmonary disease. Pulmonary surfactant protein (SP)-D modulates immune and inflammatory responses in the lung. We have shown previously that SP-D plays a protective role in a mouse model of allergic airway inflammation. Here we studied the role and regulation of SP-D in O3-induced inflammatory changes in the lung.MethodsTo evaluate the effects of O3 exposure in mouse strains with genetically different expression levels of SP-D we exposed Balb/c, C57BL/6 and SP-D knockout mice to O3 or air. BAL cellular and cytokine content and SP-D levels were evaluated and compared between the different strains. The kinetics of SP-D production and inflammatory parameters were studied at 0, 2, 6, 12, 24, 48, and 72 hrs after O3 exposure. The effect of IL-6, an O3-inducible cytokine, on the expression of SP-D was investigated in vitro using a primary alveolar type II cell culture.ResultsOzone-exposed Balb/c mice demonstrated significantly enhanced acute inflammatory changes including recruitment of inflammatory cells and release of KC and IL-12p70 when compared with age- and sex-matched C57BL/6 mice. On the other hand, C57BL/6 mice had significantly higher levels of SP-D and released more IL-10 and IL-6. Increase in SP-D production coincided with the resolution of inflammatory changes. Mice deficient in SP-D had significantly higher numbers of inflammatory cells when compared to controls supporting the notion that SP-D has an anti-inflammatory function in our model of O3 exposure. IL-6, which was highly up-regulated in O3 exposed mice, was capable of inducing the expression of SP-D in vitro in a dose dependent manner.ConclusionOur data suggest that IL-6 contributes to the up-regulation of SP-D after acute O3 exposure and elevation of SP-D in the lung is associated with the resolution of inflammation. Absence or low levels of SP-D predispose to enhanced inflammatory changes following acute oxidative stress.
Highlights
Ozone (O3), a common air pollutant, induces exacerbation of asthma and chronic obstructive pulmonary disease
A relative surfactant protein (SP)-D deficiency in Balb/c mice was associated with exaggerated inflammatory changes 6 hrs after O3 exposure We have previously reported that Surfactant protein-D (SP-D) levels in Balb/c and C57BL/6 mice differ under normal conditions as well as upon allergen sensitization and challenge [13]
Six hours after O3 exposure, the amount of SP-D recovered from the Bronchoalveolar lavage (BAL) was significantly lower in Balb/c mice compared with C57BL/6 mice (p = 0.0027)
Summary
Ozone (O3), a common air pollutant, induces exacerbation of asthma and chronic obstructive pulmonary disease. Pulmonary surfactant protein (SP)-D modulates immune and inflammatory responses in the lung. We studied the role and regulation of SPD in O3-induced inflammatory changes in the lung. O3 is associated with an immediate impairment of lung function and contributes to increased morbidity in patients with asthma and chronic obstructive pulmonary disease (COPD) [1,2]. Short-term exposure to O3 increases levels of the vascular adhesion molecules P-selectin and ICAM-1 in airway lavages and bronchial tissue and induces influx of neutrophils and mast cells [3]. Some strains like 129/J and DBA/2J respond with an early peak of polymorphonuclear cells six hours after exposure, whereas C57BL/6J mice reach the peak of inflammation 24 hrs after exposure. The mechanisms influencing the severity of the O3-induced pulmonary reaction and the molecules involved in the modulation of this response are yet to be fully determined
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