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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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Related in: MedlinePlus

EPO is vital for Mp killing mechanisms in vitro and in vivo.A) Purified human EPO (0.5 µM) was added to Mp (5×106) and viability was assessed over the course of 1 hr. **p<.01,*p<.05. n = 3 experiments. B) Mice were treated with Ova and Mp (O+Mp) as previously described but 2 hrs prior to Mp infection, some mice were given either vehicle (V) or resorcinol (R). Mice were given boosters after 24 hrs and samples harvested at 72 hrs for Mp burden. *p<.05. n = 2 experiments (8–10 mice/group).
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pone-0032436-g007: EPO is vital for Mp killing mechanisms in vitro and in vivo.A) Purified human EPO (0.5 µM) was added to Mp (5×106) and viability was assessed over the course of 1 hr. **p<.01,*p<.05. n = 3 experiments. B) Mice were treated with Ova and Mp (O+Mp) as previously described but 2 hrs prior to Mp infection, some mice were given either vehicle (V) or resorcinol (R). Mice were given boosters after 24 hrs and samples harvested at 72 hrs for Mp burden. *p<.05. n = 2 experiments (8–10 mice/group).

Mentions: Our in vivo data suggests that the presence of SP-A appears to interfere with eosinophil mediated killing of Mp and our in vitro data suggests that one mechanism through which SP-A exerts this affect is by binding eosinophils and limiting EPO release when they encounter Mp. Therefore, to determine if EPO can directly kill Mp, purified EPO was added to Mp cultures for 1 hour and Mp viability was assessed. When used at a similar concentration (0.5 µM) reported to kill M. tuberculosis[18], EPO killing of Mp appears to be rapid, with 75% of the pathogen eliminated in the first 30 minutes of incubation (fig. 7A).


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)

EPO is vital for Mp killing mechanisms in vitro and in vivo.A) Purified human EPO (0.5 µM) was added to Mp (5×106) and viability was assessed over the course of 1 hr. **p<.01,*p<.05. n = 3 experiments. B) Mice were treated with Ova and Mp (O+Mp) as previously described but 2 hrs prior to Mp infection, some mice were given either vehicle (V) or resorcinol (R). Mice were given boosters after 24 hrs and samples harvested at 72 hrs for Mp burden. *p<.05. n = 2 experiments (8–10 mice/group).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0032436-g007: EPO is vital for Mp killing mechanisms in vitro and in vivo.A) Purified human EPO (0.5 µM) was added to Mp (5×106) and viability was assessed over the course of 1 hr. **p<.01,*p<.05. n = 3 experiments. B) Mice were treated with Ova and Mp (O+Mp) as previously described but 2 hrs prior to Mp infection, some mice were given either vehicle (V) or resorcinol (R). Mice were given boosters after 24 hrs and samples harvested at 72 hrs for Mp burden. *p<.05. n = 2 experiments (8–10 mice/group).
Mentions: Our in vivo data suggests that the presence of SP-A appears to interfere with eosinophil mediated killing of Mp and our in vitro data suggests that one mechanism through which SP-A exerts this affect is by binding eosinophils and limiting EPO release when they encounter Mp. Therefore, to determine if EPO can directly kill Mp, purified EPO was added to Mp cultures for 1 hour and Mp viability was assessed. When used at a similar concentration (0.5 µM) reported to kill M. tuberculosis[18], EPO killing of Mp appears to be rapid, with 75% of the pathogen eliminated in the first 30 minutes of incubation (fig. 7A).

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