Abstract

The surfactant protein (SP-A) receptor SP-R210 has been shown to increase phagocytosis of SP-A-bound pathogens and to modulate cytokine secretion by immune cells. SP-A plays an important role in pulmonary immunity by enhancing opsonization and clearance of pathogens and by modulating macrophage inflammatory responses. Alternative splicing of the Myo18Agene results in two isoforms: SP-R210S and SP-R210L, with the latter predominantly expressed in alveolar macrophages. In this study we show that SP-A is required for optimal expression of SP-R210L on alveolar macrophages. Interestingly, pre-treatment with SP-A prepared by different methods either enhances or suppresses responsiveness to LPS, possibly due to differential co-isolation of SP-B or other proteins. We also report that dominant negative disruption of SP-R210L augments expression of receptors including SR-A, CD14, and CD36, and enhances macrophages' inflammatory response to TLR stimulation. Finally, because SP-A is known to modulate CD14, we used a variety of techniques to investigate how SP-R210 mediates the effect of SP-A on CD14. These studies revealed a novel physical association between SP-R210S, CD14, and SR-A leading to an enhanced response to LPS, and found that SP-R210L and SP-R210S regulate internalization of CD14 via distinct macropinocytosis-like mechanisms. Together, our findings support a model in which SP-R210 isoforms differentially regulate trafficking, expression, and activation of innate immune receptors on macrophages.

Original languageEnglish (US)
Article numbere0126576
JournalPloS one
Volume10
Issue number5
DOIs
StatePublished - May 12 2015

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Macrophage Activation
Macrophages
Modulators
Protein Isoforms
macrophages
Chemical activation
Alveolar Macrophages
Pathogens
Alternative Splicing
Phagocytosis
Surface-Active Agents
inflammation
Immunity
receptors
Association reactions
pathogens
Cytokines
Proteins
alternative splicing
Lung

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Yang, L., Carrillo, M., Wu, Y. M., DiAngelo, S. L., Silveyra, P., Umstead, T. M., ... Chroneos, Z. C. (2015). SP-R210 (Myo18A) isoforms as intrinsic modulators of macrophage priming and activation. PloS one, 10(5), [e0126576]. https://doi.org/10.1371/journal.pone.0126576
Yang, Linlin ; Carrillo, Marykate ; Wu, Yuchieh M. ; DiAngelo, Susan L. ; Silveyra, Patricia ; Umstead, Todd M. ; Halstead, E. Scott ; Davies, Michael L. ; Hu, Sanmei ; Floros, Joanna ; McCormack, Francis X. ; Christensen, Neil D. ; Chroneos, Zissis C. / SP-R210 (Myo18A) isoforms as intrinsic modulators of macrophage priming and activation. In: PloS one. 2015 ; Vol. 10, No. 5.
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title = "SP-R210 (Myo18A) isoforms as intrinsic modulators of macrophage priming and activation",
abstract = "The surfactant protein (SP-A) receptor SP-R210 has been shown to increase phagocytosis of SP-A-bound pathogens and to modulate cytokine secretion by immune cells. SP-A plays an important role in pulmonary immunity by enhancing opsonization and clearance of pathogens and by modulating macrophage inflammatory responses. Alternative splicing of the Myo18Agene results in two isoforms: SP-R210S and SP-R210L, with the latter predominantly expressed in alveolar macrophages. In this study we show that SP-A is required for optimal expression of SP-R210L on alveolar macrophages. Interestingly, pre-treatment with SP-A prepared by different methods either enhances or suppresses responsiveness to LPS, possibly due to differential co-isolation of SP-B or other proteins. We also report that dominant negative disruption of SP-R210L augments expression of receptors including SR-A, CD14, and CD36, and enhances macrophages' inflammatory response to TLR stimulation. Finally, because SP-A is known to modulate CD14, we used a variety of techniques to investigate how SP-R210 mediates the effect of SP-A on CD14. These studies revealed a novel physical association between SP-R210S, CD14, and SR-A leading to an enhanced response to LPS, and found that SP-R210L and SP-R210S regulate internalization of CD14 via distinct macropinocytosis-like mechanisms. Together, our findings support a model in which SP-R210 isoforms differentially regulate trafficking, expression, and activation of innate immune receptors on macrophages.",
author = "Linlin Yang and Marykate Carrillo and Wu, {Yuchieh M.} and DiAngelo, {Susan L.} and Patricia Silveyra and Umstead, {Todd M.} and Halstead, {E. Scott} and Davies, {Michael L.} and Sanmei Hu and Joanna Floros and McCormack, {Francis X.} and Christensen, {Neil D.} and Chroneos, {Zissis C.}",
year = "2015",
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Yang, L, Carrillo, M, Wu, YM, DiAngelo, SL, Silveyra, P, Umstead, TM, Halstead, ES, Davies, ML, Hu, S, Floros, J, McCormack, FX, Christensen, ND & Chroneos, ZC 2015, 'SP-R210 (Myo18A) isoforms as intrinsic modulators of macrophage priming and activation', PloS one, vol. 10, no. 5, e0126576. https://doi.org/10.1371/journal.pone.0126576

SP-R210 (Myo18A) isoforms as intrinsic modulators of macrophage priming and activation. / Yang, Linlin; Carrillo, Marykate; Wu, Yuchieh M.; DiAngelo, Susan L.; Silveyra, Patricia; Umstead, Todd M.; Halstead, E. Scott; Davies, Michael L.; Hu, Sanmei; Floros, Joanna; McCormack, Francis X.; Christensen, Neil D.; Chroneos, Zissis C.

In: PloS one, Vol. 10, No. 5, e0126576, 12.05.2015.

Research output: Contribution to journalArticle

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T1 - SP-R210 (Myo18A) isoforms as intrinsic modulators of macrophage priming and activation

AU - Yang, Linlin

AU - Carrillo, Marykate

AU - Wu, Yuchieh M.

AU - DiAngelo, Susan L.

AU - Silveyra, Patricia

AU - Umstead, Todd M.

AU - Halstead, E. Scott

AU - Davies, Michael L.

AU - Hu, Sanmei

AU - Floros, Joanna

AU - McCormack, Francis X.

AU - Christensen, Neil D.

AU - Chroneos, Zissis C.

PY - 2015/5/12

Y1 - 2015/5/12

N2 - The surfactant protein (SP-A) receptor SP-R210 has been shown to increase phagocytosis of SP-A-bound pathogens and to modulate cytokine secretion by immune cells. SP-A plays an important role in pulmonary immunity by enhancing opsonization and clearance of pathogens and by modulating macrophage inflammatory responses. Alternative splicing of the Myo18Agene results in two isoforms: SP-R210S and SP-R210L, with the latter predominantly expressed in alveolar macrophages. In this study we show that SP-A is required for optimal expression of SP-R210L on alveolar macrophages. Interestingly, pre-treatment with SP-A prepared by different methods either enhances or suppresses responsiveness to LPS, possibly due to differential co-isolation of SP-B or other proteins. We also report that dominant negative disruption of SP-R210L augments expression of receptors including SR-A, CD14, and CD36, and enhances macrophages' inflammatory response to TLR stimulation. Finally, because SP-A is known to modulate CD14, we used a variety of techniques to investigate how SP-R210 mediates the effect of SP-A on CD14. These studies revealed a novel physical association between SP-R210S, CD14, and SR-A leading to an enhanced response to LPS, and found that SP-R210L and SP-R210S regulate internalization of CD14 via distinct macropinocytosis-like mechanisms. Together, our findings support a model in which SP-R210 isoforms differentially regulate trafficking, expression, and activation of innate immune receptors on macrophages.

AB - The surfactant protein (SP-A) receptor SP-R210 has been shown to increase phagocytosis of SP-A-bound pathogens and to modulate cytokine secretion by immune cells. SP-A plays an important role in pulmonary immunity by enhancing opsonization and clearance of pathogens and by modulating macrophage inflammatory responses. Alternative splicing of the Myo18Agene results in two isoforms: SP-R210S and SP-R210L, with the latter predominantly expressed in alveolar macrophages. In this study we show that SP-A is required for optimal expression of SP-R210L on alveolar macrophages. Interestingly, pre-treatment with SP-A prepared by different methods either enhances or suppresses responsiveness to LPS, possibly due to differential co-isolation of SP-B or other proteins. We also report that dominant negative disruption of SP-R210L augments expression of receptors including SR-A, CD14, and CD36, and enhances macrophages' inflammatory response to TLR stimulation. Finally, because SP-A is known to modulate CD14, we used a variety of techniques to investigate how SP-R210 mediates the effect of SP-A on CD14. These studies revealed a novel physical association between SP-R210S, CD14, and SR-A leading to an enhanced response to LPS, and found that SP-R210L and SP-R210S regulate internalization of CD14 via distinct macropinocytosis-like mechanisms. Together, our findings support a model in which SP-R210 isoforms differentially regulate trafficking, expression, and activation of innate immune receptors on macrophages.

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Yang L, Carrillo M, Wu YM, DiAngelo SL, Silveyra P, Umstead TM et al. SP-R210 (Myo18A) isoforms as intrinsic modulators of macrophage priming and activation. PloS one. 2015 May 12;10(5). e0126576. https://doi.org/10.1371/journal.pone.0126576