Abstract
BackgroundIncreased exposure to Ozone (O3) is associated with adverse health effects in individuals afflicted with respiratory diseases. Surfactant protein-A (SP-A), encoded by SP-A1 and SP-A2, is the largest protein component in pulmonary surfactant and is functionally impaired by O3-oxidation.ObjectiveWe used humanized SP-A2 transgenic mice with allelic variation corresponding to a glutamine (Q) to lysine (K) amino acid substitution at position 223 in the lectin domain to determine the impact of this genetic variation in regards to O3 exposure.MethodsMice were exposed to 2ppm O3 or Filtered Air (FA) for 3 hours and 24 hrs post-challenge pulmonary function tests and other parameters associated with inflammation were assessed in the bronchoalveolar lavage (BAL) fluid and lung tissue. Additionally, mouse tracheal epithelial cells were cultured and TEER measurements recorded for each genotype to determine baseline epithelial integrity.ResultsCompared to FA, O3 exposure led to significantly increased sensitivity to methacholine challenge in all groups of mice. SP-A2 223Q variant mice were significantly protected from O3-induced AHR compared to SP-A-/- and SP-A2 223K mice. Neutrophilia was observed in all genotypes of mice post O3-exposure, however, SP-A2 223Q mice had a significantly lower percentage of neutrophils compared to SP-A-/- mice. Albumin levels in BAL were unchanged in O3-exposed SP-A2 223Q mice compared to their FA controls, while levels were significantly increased in all other genotypes of O3-exposed mice. SP-A 223Q MTECS has significant higher TEER values than all other genotypes, and WT MTECS has significantly higher TEER than the SP-A KO and SP-A 223K MTECS.SignificanceTaken together, our study suggests that expression of a glutamine (Q) as position 223 in SP-A2, as opposed to expression of lysine (K), is more protective in acute exposures to ozone and results in attenuated O3-induced AHR, neutrophilia, and vascular permeability.
Highlights
Air pollution has become a critical problem for climate change and global conservation efforts, and for public health [1]
Albumin levels in bronchoalveolar lavage (BAL) were unchanged in O3-exposed SP-A2 223Q mice compared to their Filtered Air (FA) controls, while levels were significantly increased in all other genotypes of O3-exposed mice
While many publications highlight a role for Surfactant protein-A (SP-A) in host defense against pathogens, SP-A has been described as an important mediator in a variety of diseases including cystic fibrosis [17, 18], allergic rhinitis [19], sinusitis [20], lung cancer metastasis [21], pulmonary fibrosis [22], and more recently asthma ([3, 23, 24]) and COPD [25, 26]
Summary
Increased exposure to Ozone (O3) is associated with adverse health effects in individuals afflicted with respiratory diseases. Surfactant protein-A (SP-A), encoded by SP-A1 and SPA2, is the largest protein component in pulmonary surfactant and is functionally impaired by O3-oxidation
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