Journal article
Free actin impairs macrophage bacterial defenses via scavenger receptor MARCO interaction with reversal by plasma gelsolin
American journal of physiology. Lung cellular and molecular physiology, Vol.312(6), pp.L1018-L1028
06/01/2017
DOI: 10.1152/ajplung.00067.2017
PMCID: PMC5495953
PMID: 28385809
Abstract
Lung injury can release intracellular actin into the alveolar milieu and is also associated with increased susceptibility to secondary infections. We investigated the effect of free (extracellular) actin on lung macrophage host defense functions. Western blot analysis demonstrated free actin release into the lung lavage fluids of mouse models of ozone injury, influenza infection, and secondary pneumococcal pneumonia and in samples from patients following burn and inhalation injury. Using levels comparable with those observed in lung injury, we found that free actin markedly inhibited murine lung macrophage binding and uptake in vitro of
,
, and
, (e.g.,
, mean %inhibition, actin vs. vehicle: 85 ± 0.3 (SD);
= 22,
< .001). Similar effects were observed on the ability of primary human macrophages to bind and ingest fluorescent
(~75% inhibition). Plasma gelsolin (pGSN), a protein that functions to bind and cleave actin, restored bacterial binding and uptake by both murine and human macrophages. Scavenger receptor inhibitors reduced binding of fluorescent actin by murine macrophages [fluorescence index (×10
) after incubation with vehicle, actin, or actin + polyinosinic acid, respectively: 0.8 ± 0.7, 101.7 ± 50.7, or 52.7 ± 16.9;
= 5-6,
< 0.05]. In addition, actin binding was reduced in a MARCO/SR-AI/II-deficient cell line and by normal AMs obtained from MARCO
mice. After release from injured cells during lung injury, free actin likely contributes to impaired host defense by blocking scavenger receptor binding of bacteria. This mechanism for increased risk of secondary infections after lung injury or inflammation may represent another target for therapeutic intervention with pGSN.
Details
- Title: Subtitle
- Free actin impairs macrophage bacterial defenses via scavenger receptor MARCO interaction with reversal by plasma gelsolin
- Creators
- Christine M Ordija - Harvard UniversityTerry Ting-Yu Chiou - Harvard UniversityZhiping Yang - Harvard UniversityGlen M Deloid - Harvard UniversityMelina de Oliveira Valdo - Harvard UniversityZhi Wang - Harvard UniversityAlice Bedugnis - Harvard UniversityTerry L Noah - University of North Carolina at Chapel HillSamuel Jones - University of North Carolina at Chapel HillHenry Koziel - Beth Israel Deaconess Medical CenterLester Kobzik - Harvard University
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.312(6), pp.L1018-L1028
- DOI
- 10.1152/ajplung.00067.2017
- PMID
- 28385809
- PMCID
- PMC5495953
- NLM abbreviation
- Am J Physiol Lung Cell Mol Physiol
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Grant note
- R01 HL115778 / NHLBI NIH HHS P30 ES000002 / NIEHS NIH HHS T32 HL007118 / NHLBI NIH HHS
- Language
- English
- Date published
- 06/01/2017
- Academic Unit
- Surgery
- Record Identifier
- 9984756263502771
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