SP-R210 (Myo18A) Isoforms as Intrinsic Modulators of Macrophage Priming and Activation.
PLoS One
; 10(5): e0126576, 2015.
Article
em En
| MEDLINE
| ID: mdl-25965346
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 Myo18A gene 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Miosinas
/
Macrófagos Alveolares
/
Receptores de Lipopolissacarídeos
/
Proteína A Associada a Surfactante Pulmonar
/
Inflamação
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos