Surfactant protein-A enhances respiratory syncytial virus clearance in vivo

LeVine, Ann Marie; Gwozdz, Jodie; Stark, James M.; Bruno, Michael D.; Whitsett, Jeffrey A.; Korfhagen, Thomas R.

doi:10.1172/jci5849

Cited by 263 publications

(196 citation statements)

References 46 publications

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“…Carbohydrate recognition and opsonization of viruses may be an important role of SP-A in viral clearance. Lung inflammation and the viral titers in lung homogenates 3 days after the administration of RSV were significantly increased in SP-A -/-mice [13]. We consider that the present study is not inconsistent with the concept that SP-A plays an important role in RSV clearance.…”

Section: Discussioncontrasting

confidence: 47%

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Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

et al. 2003

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Surfactant protein A (SP-A) and lactoferrin (LF) play important roles in innate immune systems in the respiratory mucous membranes. We investigated how SP-A and LF act against respiratory syncytial virus (RSV) infection. The present study indicated that RSV-induced IL-8 secretion from HEp-2 cells was up-regulated by SP-A (170% of control) but downregulated by LF (23% of control). RSV infectivity determined by viral titers and the uptake of FITC-labeled RSV were also increased by SP-A, but decreased by LF. To clarify the mechanism of these opposite effects, we examined the interactions of SP-A and LF with RSV F protein, the most important surface glycoprotein for viral penetration. RSV F protein was found to be the ligand for both SP-A and LF, but the manners of binding were different. LF directly interacted with the F 1 subunit, which involved antigenic sites of F protein. Contrarily, SP-A associated with the F 2 subunit, which was highly glycosylated. SP-A but not LF failed to interact with deglycosylated F protein. Moreover, SP-A initiated the hemolyzing fusion activity of F protein. These results suggest that SP-A and LF modulate RSV infection by different binding specificity to F protein.

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Section: Discussioncontrasting

confidence: 47%

“…Animals lacking SP-A exhibit reduced bacterial clearance and elevated pulmonary inflammation in response to microbial challenge [10][11][12]. The clearance of RSV was also impaired in SP-A -/-mice [13], but the precise mechanism by which SP-A alters RSV infection has not been clearly clarified.…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

et al. 2003

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“…Furthermore, in contrast to SP-D deficiency, SP-A deficiency was associated with decreased hydrogen peroxide production by isolated alveolar macrophages (22).…”

Section: Discussionmentioning

confidence: 94%

Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice

Wert

Yoshida

LeVine

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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383

298

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Targeted ablation of the surfactant protein D (SP-D) gene caused chronic inflammation, emphysema, and fibrosis in the lungs of SP-D (؊͞؊) mice. Although lung morphology was unperturbed during the first 2 weeks of life, airspace enlargement was observed by 3 weeks and progressed with advancing age. Inflammation consisted of hypertrophic alveolar macrophages and peribronchiolar-perivascular monocytic infiltrates. These abnormalities were associated with increased activity of the matrix metalloproteinases, MMP2 and MMP9, and immunostaining for MMP9 and MMP12 in alveolar macrophages. Hydrogen peroxide production by isolated alveolar macrophages also was increased significantly (10-fold). SP-D plays a critical role in the suppression of alveolar macrophage activation, which may contribute to the pathogenesis of chronic inflammation and emphysema.

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“…Like mannose-binding protein, the pulmonary collectins SP-A and SP-D can bind and aggregate pathogens (bacteria, fungi, and viruses), thereby enhancing phagocytosis and killing by immune cells. Consistent with their ability to opsonize pathogens, clearance of bacteria, fungi, and viruses is defective in SP-A-deficient mice, and is associated with enhanced inflammation (25,35,36). SP-D-deficient mice also show defects in fungal and viral clearance, but they still have some capacity to clear bacteria (24,37).…”

Section: Discussionmentioning

confidence: 99%

Neonatal Hyperoxia Enhances the Inflammatory Response in Adult Mice Infected with Influenza A Virus

O’Reilly

Marr

Yee

et al. 2008

Am J Respir Crit Care Med

112

124

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Rationale: Lungs of adult mice exposed to hyperoxia as newborns are simplified and exhibit reduced function much like that observed in people who had bronchopulmonary dysplasia (BPD) as infants. Because survivors of BPD also show increased risk for symptomatic respiratory infections, we investigated how neonatal hyperoxia affected the response of adult mice infected with influenza A virus infection. Objectives: To determine whether neonatal hyperoxia increased the severity of influenza A virus infection in adult mice. Methods: Adult female mice exposed to room air or hyperoxia between Postnatal Days 1 and 4 were infected with a sublethal dose of influenza A virus. Measurements and Main Results: The number of macrophages, neutrophils, and lymphocytes observed in airways of infected mice that had been exposed to hyperoxia as neonates was significantly greater than in infected siblings that had been exposed to room air. Enhanced inflammation correlated with increased levels of monocyte chemotactic protein-1 (CCL2) in lavage fluid, whereas infectionassociated changes in IFN-g, IL-1b, IL-6, tumor necrosis factor-a, KC, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein-1a, and production of virus-specific antibodies, were largely unaffected. Increased mortality of mice exposed to neonatal hyperoxia occurred by Day 14 of infection, and was associated with persistent inflammation and fibrosis. Conclusions: These data suggest that the disruptive effect of hyperoxia on neonatal lung development also reprograms key innate immunoregulatory pathways in the lung, which may contribute to exacerbated pathology and poorer resistance to respiratory viral infections typically seen in people who had BPD.

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Surfactant protein-A enhances respiratory syncytial virus clearance in vivo

Cited by 263 publications

References 46 publications

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice

Neonatal Hyperoxia Enhances the Inflammatory Response in Adult Mice Infected with Influenza A Virus

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