Evidence map›Paper›PMID 26998217›Full record

ArticleBiology of sex differences2016

Single-cell analysis reveals differential regulation of the alveolar macrophage actin cytoskeleton by surfactant proteins A1 and A2: implications of sex and aging.

Nikolaos Tsotakos, David S Phelps, Christopher M Yengo, Vernon M Chinchilli, Joanna Floros

Open access · goldAbstract read
In one paragraph

Article in Biology of sex differences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 27 citations in OpenAlex.

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  8. How cell migration helps immune sentinels.Frontiers in cell and developmental biology · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Nikolaos TsotakosCenter for Host Defense, Inflammation and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Rm. C4752, H085, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 USA.
David S PhelpsCenter for Host Defense, Inflammation and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Rm. C4752, H085, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 USA.
Christopher M YengoDepartment of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA USA.
Vernon M ChinchilliDepartment of Public Health Sciences, The Pennsylvania State University College of Medicine, Hershey, PA USA.
Joanna FlorosCenter for Host Defense, Inflammation and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Rm. C4752, H085, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 USA ; Department of Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, Hershey, PA USA.
Pennsylvania State University · US

Funding

SURFACTANT PROTEINS AND RESPIRATORY DISTRESS SYNDROMER37HL034788 · NHLBI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI FLOROS, JOANNA · 1996 to 2005
$3.2M
SURFACTANT PROTEINS AND RESPIRATORY DISTRESS SYNDROMER01HL034788 · NHLBI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI FLOROS, JOANNA · 1985 to 2011
$3.0M
NHLBI NIH HHS R01 HL034788NHLBI NIH HHS R37 HL034788
6 · The paper itself

Abstract

backgroundSurfactant protein A (SP-A) contributes to lung immunity by regulating inflammation and responses to microorganisms invading the lung. The huge genetic variability of SP-A in humans implies that this protein is highly important in tightly regulating the lung immune response. Proteomic studies have demonstrated that there are differential responses of the macrophages to SP-A1 and SP-A2 and that there are sex differences implicated in these responses.

methodsPurified SP-A variants were used for administration to alveolar macrophages from SP-A knockout (KO) mice for in vitro studies, and alveolar macrophages from humanized SP-A transgenic mice were isolated for ex vivo studies. The actin cytoskeleton was examined by fluorescence and confocal microscopy, and the macrophages were categorized according to the distribution of polymerized actin.

resultsIn accordance with previous data, we report that there are sex differences in the response of alveolar macrophages to SP-A1 and SP-A2. The cell size and F-actin content of the alveolar macrophages are sex- and age-dependent. Importantly, there are different subpopulations of cells with differential distribution of polymerized actin. In vitro, SP-A2 destabilizes actin in female, but not male, mice, and the same tendency is observed by SP-A1 in cells from male mice. Similarly, there are differences in the distribution of AM subpopulations isolated from SP-A transgenic mice depending on sex and age.

conclusionsThere are marked sex- and age-related differences in the alveolar macrophage phenotype as illustrated by F-actin staining between SP-A1 and SP-A2. Importantly, the phenotypic switch caused by the different SP-A variants is subtle, and pertains to the frequency of the observed subpopulations, demonstrating the need for single-cell analysis approaches. The differential responses of alveolar macrophages to SP-A1 and SP-A2 highlight the importance of genotype in immune regulation and the susceptibility to lung disease and the need for development of individualized treatment options.

Indexed as

Actin cytoskeletonAge-related differencesAlveolar macrophagesF-actinG-actinImmune responseSex differencesSingle-cell imaging analysisSurfactant protein A

Identifiers

PMID26998217
PMCPMC4797174
OpenAlexW2307965051

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.