Evidence map›Paper›PMID 26445168›Full record

ArticlePloS one2015

ERK Signaling Is Essential for Macrophage Development.

Edward T Richardson, Supriya Shukla, Nancy Nagy, W Henry Boom, Rose C Beck, Lan Zhou, Gary E Landreth, Clifford V Harding

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

43 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Anti-inflammatory and polarization-modulating effects ofJournal of traditional and complementary medicine · 2026
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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

8 authors at 2 institutions in 1 country.

Edward T RichardsonDepartment of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Medical Scientist Training Program, Case Western Reserve University, Cleveland, Ohio, United States of America.
Supriya ShuklaDepartment of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Nancy NagyDepartment of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
W Henry BoomDivision of Infectious Diseases and HIV Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Center for AIDS Research, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Rose C BeckDepartment of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Lan ZhouDepartment of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Gary E LandrethDepartment of Neurosciences, Case Western Reserve University, Cleveland, Ohio, United States of America.
Clifford V HardingDepartment of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Division of Infectious Diseases and HIV Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Center for AIDS Research, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Case Western Reserve University · USUniversity Hospitals Case Medical Center · US

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Regulation of macrophages by Mycobacterium tuberculosisR01AI034343 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 1994 to 2017
$6.2M
HETEROGENEITY OF TCELLS IN M TUBERCULOSIS INFECTIONR01AI027243 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI BOOM, W. HENRY · 1989 to 2016
$5.5M
Targeting Notch2 in Hematopoietic Cell Therapy.R01HL103827 · NHLBI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI ZHOU, LAN · 2012 to 2022
$4.3M
Immunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4M
NCI NIH HHS P30 CA043703NHLBI NIH HHS R01 HL103827NIAID NIH HHS R01 AI027243NIAID NIH HHS R01 AI034343NIAID NIH HHS T32 AI089474NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

Macrophages depend on colony stimulating factor 1 (also known as M-CSF) for their growth and differentiation, but the requirements for intracellular signals that lead to macrophage differentiation and function remain unclear. M-CSF is known to activate ERK1 and ERK2, but the importance of this signaling pathway in macrophage development is unknown. In these studies, we characterized a novel model of Erk1(-/-) Erk2(flox/flox) Lyz2(Cre/Cre) mice in which the ERK2 isoform is deleted from macrophages in the background of global ERK1 deficiency. Cultures of M-CSF-stimulated bone marrow precursors from these mice yielded reduced numbers of macrophages. Whereas macrophages developing from M-CSF-stimulated bone marrow of Erk2(flox/flox) Lyz2(Cre/Cre) mice showed essentially complete loss of ERK2 expression, the reduced number of macrophages that develop from Erk1(-/-) Erk2(flox/flox) Lyz2(Cre/Cre) bone marrow show retention of ERK2 expression, indicating selective outgrowth of a small proportion of precursors in which Cre-mediated deletion failed to occur. The bone marrow of Erk1(-/-) Erk2(flox/flox) Lyz2(Cre/Cre) mice was enriched for CD11b+ myeloid cells, CD11b(hi) Gr-1(hi) neutrophils, Lin- c-Kit+ Sca-1+ hematopoietic stem cells, and Lin- c-Kit+ CD34+ CD16/32+ granulocyte-macrophage progenitors. Culture of bone marrow Lin- cells under myeloid-stimulating conditions yielded reduced numbers of monocytes. Collectively, these data indicate that the defect in production of macrophages is not due to a reduced number of progenitors, but rather due to reduced ability of progenitors to proliferate and produce macrophages in response to M-CSF-triggered ERK signaling. Macrophages from Erk1(-/-) Erk2(flox/flox) Lyz2(Cre/Cre) bone marrow showed reduced induction of M-CSF-regulated genes that depend on the ERK pathway for their expression. These data demonstrate that ERK1/ERK2 play a critical role in driving M-CSF-dependent proliferation of bone marrow progenitors for production of macrophages.

Indexed as

MAP Kinase Signaling SystemAnimalsBone Marrow CellsCell DifferentiationCell ProliferationCells, CulturedGene DeletionGene Expression RegulationGranulocytesHematopoiesisMacrophage Colony-Stimulating FactorMacrophagesMiceMice, Inbred C57BLMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Macrophage Colony-Stimulating FactorMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3

Identifiers

PMID26445168
PMCPMC4596867
OpenAlexW2175500475

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.