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Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.

Ledford JG, Mukherjee S, Kislan MM, Nugent JL, Hollingsworth JW, Wright JR - PLoS ONE (2012)

Bottom Line: Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products.In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity.These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation and damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America. j.ledford@cellbio.duke.edu

ABSTRACT
Surfactant protein-A (SP-A) has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp) frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT) and SP-A(-/-) allergic mice challenged with the model antigen ovalbumin (Ova) that were concurrently infected with Mp (Ova+Mp) to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp) as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO), which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A(-/-) mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation and damage.

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SP-A is protective against Mp-induced allergic pathologies.A) PAS stained lung sections examined at 10× magnification were B) blindly scored for mucus production with 0 representing no mucus present and 5 being mucus present in greater than 75% of airways and bronchioles. C) H&E stained lung sections shows inflammation and RBCs in alveolar spaces and lymphatics of Ova+Mp treated mice. D) Albumin measured in the BAL as a measure of lung damage and vascular permeability. n = representative of 3 experiments, *p<.05.
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pone-0032436-g008: SP-A is protective against Mp-induced allergic pathologies.A) PAS stained lung sections examined at 10× magnification were B) blindly scored for mucus production with 0 representing no mucus present and 5 being mucus present in greater than 75% of airways and bronchioles. C) H&E stained lung sections shows inflammation and RBCs in alveolar spaces and lymphatics of Ova+Mp treated mice. D) Albumin measured in the BAL as a measure of lung damage and vascular permeability. n = representative of 3 experiments, *p<.05.

Mentions: A part of the immune response to Mp infection in an allergic airway is dramatically heightened mucus production by goblet cells. While PAS stained cells were increased in Ova treated and in Mp-infected Ova treated airways of both WT and SP-A−/− mice as compared to saline controls, SP-A−/− mice had significantly more PAS positive cells evident even in large airways and distal bronchioles compared to WT mice in each of the treatment groups (fig. 8A,B). Resorcinol treatment did not affect the percentage of PAS positive cells in the large airways (data not shown). In conjunction with our previous data presented in this manuscript, this indicates there is no correlation between Mp burden and mucus production in the large airway in our mouse model.


Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.

Ledford JG, Mukherjee S, Kislan MM, Nugent JL, Hollingsworth JW, Wright JR - PLoS ONE (2012)

SP-A is protective against Mp-induced allergic pathologies.A) PAS stained lung sections examined at 10× magnification were B) blindly scored for mucus production with 0 representing no mucus present and 5 being mucus present in greater than 75% of airways and bronchioles. C) H&E stained lung sections shows inflammation and RBCs in alveolar spaces and lymphatics of Ova+Mp treated mice. D) Albumin measured in the BAL as a measure of lung damage and vascular permeability. n = representative of 3 experiments, *p<.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285686&req=5

pone-0032436-g008: SP-A is protective against Mp-induced allergic pathologies.A) PAS stained lung sections examined at 10× magnification were B) blindly scored for mucus production with 0 representing no mucus present and 5 being mucus present in greater than 75% of airways and bronchioles. C) H&E stained lung sections shows inflammation and RBCs in alveolar spaces and lymphatics of Ova+Mp treated mice. D) Albumin measured in the BAL as a measure of lung damage and vascular permeability. n = representative of 3 experiments, *p<.05.
Mentions: A part of the immune response to Mp infection in an allergic airway is dramatically heightened mucus production by goblet cells. While PAS stained cells were increased in Ova treated and in Mp-infected Ova treated airways of both WT and SP-A−/− mice as compared to saline controls, SP-A−/− mice had significantly more PAS positive cells evident even in large airways and distal bronchioles compared to WT mice in each of the treatment groups (fig. 8A,B). Resorcinol treatment did not affect the percentage of PAS positive cells in the large airways (data not shown). In conjunction with our previous data presented in this manuscript, this indicates there is no correlation between Mp burden and mucus production in the large airway in our mouse model.

Bottom Line: Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products.In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity.These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation and damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America. j.ledford@cellbio.duke.edu

ABSTRACT
Surfactant protein-A (SP-A) has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp) frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT) and SP-A(-/-) allergic mice challenged with the model antigen ovalbumin (Ova) that were concurrently infected with Mp (Ova+Mp) to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp) as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO), which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A(-/-) mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation and damage.

Show MeSH
Related in: MedlinePlus