Evidence map›Paper›PMID 21670312›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2011

Endoplasmic reticulum calcium depletion impacts chaperone secretion, innate immunity, and phagocytic uptake of cells.

Larry Robert Peters, Malini Raghavan

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

65 citing papers in PubMed, 96 citations in OpenAlex.

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  4. Macrophages release neuraminidase and cleaved calreticulin for programmed cell removal.Proceedings of the National Academy of Sciences of the United States of America · 2025
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5 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

Larry Robert PetersGraduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Malini Raghavan
University of Michigan–Ann Arbor · US

Funding

PUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5M
Vector CoreP30AR048310 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOX, DAVID ALAN · 2001 to 2010
$5.9M
Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
Calreticulin's functions in the adaptive immune responseR01AI066131 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAGHAVAN, MALINI · 2007 to 2010
$1.7M
NIAID NIH HHS AI066131NIAID NIH HHS R01 AI066131NIAMS NIH HHS P30 AR048310NIDDK NIH HHS P60 DK020572NIDDK NIH HHS P60 DK20572NIGMS NIH HHS T32 GM145304
6 · The paper itself

Abstract

A number of immunological functions are ascribed to cell surface-expressed forms of the endoplasmic reticulum (ER) chaperone calreticulin (CRT). In this study, we examined the impact of ER stress-inducing drugs upon cell surface CRT induction and the resulting immunological consequences. We showed that cell surface expression of CRT and secretion of CRT, BiP, gp96, and PDI were induced by thapsigargin (THP) treatment, which depletes ER calcium, but not by tunicamycin treatment, which inhibits protein glycosylation. Surface expression of CRT in viable, THP-treated fibroblasts correlated with their enhanced phagocytic uptake by bone marrow-derived dendritic cells. Incubation of bone marrow-derived dendritic cells with THP-treated fibroblasts enhanced sterile IL-6 production and LPS-induced generation of IL-1β, IL-12, IL-23, and TNF-α. However, extracellular CRT is not required for enhanced proinflammatory responses. Furthermore, the pattern of proinflammatory cytokine induction by THP-treated cells and cell supernatants resembled that induced by THP itself and indicated that other ER chaperones present in supernatants of THP-treated cells also do not contribute to induction of the innate immune response. Thus, secretion of various ER chaperones, including CRT, is induced by ER calcium depletion. CRT, previously suggested as an eat-me signal in dead and dying cellular contexts, can also promote phagocytic uptake of cells subject to ER calcium depletion. Finally, there is a strong synergy between calcium depletion in the ER and sterile IL-6, as well as LPS-dependent IL-1β, IL-12, IL-23, and TNF-α innate responses, findings that have implications for understanding inflammatory diseases that originate in the ER.

Indexed as

Immunity, InnateAmino Acid SequenceAnimalsBone Marrow CellsCalciumCalcium-Transporting ATPasesCalreticulinCell Line, TumorCells, CulturedDendritic CellsFibroblastsHumansInflammation MediatorsMembrane ProteinsMiceMice, Inbred BALB CCalciumCalcium-Transporting ATPasesCalreticulinInflammation MediatorsMembrane ProteinsMolecular ChaperonesThapsigargin

Identifiers

PMID21670312
PMCPMC3371385
OpenAlexW2171962012

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.