SP-R210 (Myo18A) Isoforms As Intrinsic Modulators of Macrophage Priming and Activation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 May 13

PMID 25965346

Citations 13

Authors

Linlin Yang

MaryKate Carrillo

Yuchieh M Wu

Susan L DiAngelo

Patricia Silveyra

Todd M Umstead

E Scott Halstead

Michael L Davies

Sanmei Hu

Joanna Floros

Francis X McCormack

Neil D Christensen

Zissis C Chroneos

Affiliations

Soon will be listed here.

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.

Citing Articles

Disruption of the SP-A/SP-R210 (MYO18Aα) pathway prolongs gestation and reduces fetal survival during lipopolysaccharide-induced parturition in late gestation.

Guan Z, Worth B, Umstead T, Amatya S, Booth J, Chroneos Z Am J Physiol Lung Cell Mol Physiol. 2024; 326(4):L508-L513.

PMID: 38349123 PMC: 11281786. DOI: 10.1152/ajplung.00383.2023.

SP-R210 isoforms of Myosin18A modulate endosomal sorting and recognition of influenza A virus infection in macrophages.

Yau E, Yang L, Chen Y, Umstead T, Stanley A, Halstead E Microbes Infect. 2023; 26(3):105280.

PMID: 38135024 PMC: 10948314. DOI: 10.1016/j.micinf.2023.105280.

Surfactant protein A alters endosomal trafficking of influenza A virus in macrophages.

Yau E, Yang L, Chen Y, Umstead T, Atkins H, Katz Z Front Immunol. 2023; 14:919800.

PMID: 36960051 PMC: 10028185. DOI: 10.3389/fimmu.2023.919800.

Genomic and epigenomic adaptation in SP-R210 (Myo18A) isoform-deficient macrophages.

Yau E, Chen Y, Song C, Webb J, Carillo M, Kawasawa Y Immunobiology. 2021; 226(6):152150.

PMID: 34735924 PMC: 8863115. DOI: 10.1016/j.imbio.2021.152150.

From Anti-SARS-CoV-2 Immune Response to the Cytokine Storm via Molecular Mimicry.

Kanduc D Antibodies (Basel). 2021; 10(4).

PMID: 34698069 PMC: 8544210. DOI: 10.3390/antib10040036.

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