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Cited by 101NF-κB Signaling PathwaysImmune Response and InflammationInflammation biomarkers and pathways

Functional PU.1 in macrophages has a pivotal role in NF-κB activation and neutrophilic lung inflammation during endotoxemia

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Karpurapu, Manjula, Wang, Xuerong, Deng, Jing, Park, Hyesuk, Xiao, Lei, Sadikot, Ruxana T., Frey, Randall S., Maus, Ulrich A. +3 more·2011·Blood
DOI 10.1182/blood-2011-03-341123PMC PMC3217408
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Abstract

Although the role of ETS family transcriptional factor PU.1 is well established in macrophage maturation, its role in mature macrophages with reference to sepsis- related animal model has not been elucidated. Here, we report the in vivo function of PU.1 in mediating mature macrophage inflammatory phenotype by using bone marrow chimera mice with conditional PU.1 knockout. We observed that the expression of monocyte/macrophage-specific markers CD 11b, F4/80 in fetal liver cells, and bone marrow–derived macrophages were dependent on functional PU.1. Systemic inflammation as measured in terms of NF-κB reporter activity in lung, liver, and spleen tissues was significantly decreased in PU.1-deficient chimera mice compared with wild-type chimeras on lipopolysaccharide (LPS) challenge. Unlike wild-type chimera mice, LPS challenge in PU.1-deficient chimera mice resulted in decreased lung neu-trophilic inflammation and myeloperoxidase activity. Similarly, we found attenuated inflammatory gene expression (cyclooxygenase-2, inducible nitric-oxide synthase, and TLR4) and inflammatory cytokine secretion (IL-6, MCP-1, IL-1β, TNF-α, and neutrophilic chemokine keratinocyte-derived chemokine) in PU.1-deficient mice. Most importantly, this attenuated lung and systemic inflammatory phenotype was associated with survival benefit in LPS-challenged heterozygotic PU.1-deficient mice, establishing a novel protective mechanistic role for the lineage-specific transcription factor PU.1.

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Crossref · 10.1182/blood-2011-03-341123

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  • Inactivating either 1 or 2 copies of PU.1 by fusing PU.1 with a cytoplasm-retaining estrogen receptor had no effect on the viability of alveolar macrophages.

    “inactivating either 1 copy or 2 copies of PU.1 by fusing PU.1 with cytoplasm-retaining estrogen receptor (ER) had no effect on the viability of alveolar macrophages (Karpurapu, Wang et al., 2011)”

    From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2023) · cites this paper as Karpurapu, Wang et al., 2011

  • Chronic elimination of Pu.1 KO/+ microglia occurs only in the presence of WT Pu.1 Fl/+ microglia.

    “which appears to occur only in the presence of the WT Pu.1 Fl/+ microglia, as PU.1 heterozygous mice show no difference in the viability of tissue resident macrophages (Karpurapu et al., 2011).”

    From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2023) · cites this paper as Karpurapu et al., 2011

  • The chronic elimination of Spi1KO/+ microglia occurs only in the presence of WT Spi1Fl/+ microglia.

    “which appears to occur only in the presence of the WT Spi1Fl/+ microglia, as Spi1 heterozygous mice show no difference in the viability of tissue resident macrophages (Karpurapu et al., 2011).”

    From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2025) · cites this paper as Karpurapu et al., 2011

  • Inactivating either 1 copy or 2 copies of SPI1 by fusing PU.1 with cytoplasm-retaining estrogen receptor had no effect on viability of alveolar macrophages.

    “inactivating either 1 copy or 2 copies of SPI1 by fusing PU.1 with cytoplasm-retaining estrogen receptor (ER) had no effect on the viability of alveolar macrophages (Karpurapu et al., 2011)”

    From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2025) · cites this paper as Karpurapu et al., 2011

  • Hetero- or homozygosity of PU/ER(T) allele showed no effect on the viability of alveolar macrophages.

    “Interestingly, a previous study reported that hetero- or homozygosity of PU/ER(T) allele, in which the ER ligand binding domain-G525R is fused with the full-length PU.1 to block its nuclear translocation, showed no effect on the viability of alveolar macrophages (Karpurapu et al., 2011).”

    From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2025) · cites this paper as Karpurapu et al., 2011

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Authors
Karpurapu, M., Wang, X., Deng, J., Park, H., Xiao, L., Sadikot, R. T., Frey, R. S., Maus, U. A., Park, G. Y., Scott, E. W., & Christman, J. W.
Affiliations
  • University of Illinois Chicago (US)
  • Medizinische Hochschule Hannover (DE)
  • University of Florida (US)
Corresponding author
  • Karpurapu, Manjula
  • Wang, Xuerong
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2011-11-10
Volume
118
Issue
19
Pages
5255-5266
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2011-03-341123
PMC
PMC3217408
OpenAlex
W2016208173
Cited by
101
References
47
Citations by year
2026: 5 · 2025: 13 · 2024: 7 · 2023: 12 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 6
FWCI
2.07
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01 BX000108)
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL103643, T32HL082547, R01HL075557, R01HL103643)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
PU.1, ETS transcription factors, macrophages, NF-κB activation, endotoxemia, lipopolysaccharide, sepsis, systemic inflammation, myeloperoxidase, inflammatory cytokines, keratinocyte-derived chemokine, cyclooxygenase-2, inducible nitric oxide synthase, TLR4, conditional knockout, bone marrow chimeras, survival
MeSH terms
Proto-Oncogene Protein Spi-1, Animals, Lipopolysaccharides, Macrophages, Mice, Transgenic, Neutrophils, Pneumonia, Proto-Oncogene Proteins, Trans-Activators, Immunophenotyping, NF-kappa B, Transplantation Chimera, Mice, Knockout, Endotoxemia, Mice

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