Cited by 315Immune cells in cancerPhagocytosis and Immune RegulationImmune Response and Inflammation

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Revisiting Mouse Peritoneal Macrophages: Heterogeneity, Development, and Function

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Cassado, Alexandra dos Anjos, Dâ€™ImpÃ©rio Lima, Maria Regina, Bortoluci, Karina Ramalho·2015·Frontiers in Immunology

DOI 10.3389/fimmu.2015.00225PMC PMC4437037

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Abstract

Tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop niche-specific functions. Although peritoneal macrophages are one of the best-studied macrophage populations, recently it was demonstrated the co-existence of two subsets in mouse peritoneal cavity (PerC), which exhibit distinct phenotypes, functions, and origins. These macrophage subsets have been classified, according to their morphology, as large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs). LPMs, the most abundant subset under steady state conditions, express high levels of F4/80 and low levels of class II molecules of the major histocompatibility complex (MHC). LPMs appear to be originated from embryogenic precursors, and their maintenance in PerC is regulated by expression of specific transcription factors and tissue-derived signals. Conversely, SPMs, a minor subset in unstimulated PerC, have a F4/80(low)MHC-II(high) phenotype and are generated from bone-marrow-derived myeloid precursors. In response to infectious or inflammatory stimuli, the cellular composition of PerC is dramatically altered, where LPMs disappear and SPMs become the prevalent population together with their precursor, the inflammatory monocyte. SPMs appear to be the major source of inflammatory mediators in PerC during infection, whereas LPMs contribute for gut-associated lymphoid tissue-independent and retinoic acid-dependent IgA production by peritoneal B-1 cells. In the previous years, considerable efforts have been made to broaden our understanding of LPM and SPM origin, transcriptional regulation, and functional profile. This review addresses these issues, focusing on the impact of tissue-derived signals and external stimulation in the complex dynamics of peritoneal macrophage populations.

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Figure 1 Distinct origin of peritoneal macrophage subsets. SPMs are generated from hematopoietic stem cells (HSC) in the bone marrow (BM) by differentiation of inflammatory blood monocytes (31, 40). However, LPMs appear to be originated from progenitors from yolk sac and independent of hematopoietic progenitors (69). Local proliferation of LPMs ensures homeostatic maintenance by self-renewal (36).CC BY · PubMed Central

Figure 2 Summary of the dynamic of peritoneal macrophage subsets. (A) Under homeostatic conditions, peritoneal macrophages comprise two subsets LPMs and SPMs (31). LPMs, which are the major peritoneal macrophage population, appear to be responsible for phagocytosis of apoptotic cell and tissue repair (36). (B) At the outset of inflammation, the myeloid compartment is modified in general by disappearance of LPMs, increase of SPMs numbers, and monocytes influx (31, 35, 36, 40). The changes in the myeloid cells from zymosan, T. cruzi, and LPS stimulated or thioglicollate-elicited PerC result in the gain of immune state (35, 36). SPMs from zymosan and T. cruzi stimulated mice contribute to effector function of PerC through secretion of high levels of NO and presence of IL-12-producing cells (35). In response to LPS in vivo, SPMs produce several inflammatory cytokines, such as IL-12, MIP-1α, TNF-α, and RANTES, whereas LPMs produce enhanced amounts of G-CSF, GM-CSF, and KC (36). LPMs, which migrate to omentum by a retinoic acid and GATA-6-dependent way in response to in vivo LPS stimulation or vitamin-A deprivation, return to PerC and appear to be correlated with GALT-independent and TGF-β2-dependent IgA production by B-1 cells in the intestine (40).CC BY · PubMed Central

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Affiliations: Universidade de São Paulo (BR)
Universidade Federal de São Paulo (BR)
Corresponding author: Cassado, Alexandra dos Anjos
ORCID: Cassado, Alexandra dos Anjos
Bortoluci, Karina Ramalho
Venue: Frontiers in Immunology
Publisher: Frontiers Media SA
Published: 2015-05-19
Volume: 6
Pages: 225-225
ISSN: 1664-3224 (ISSN-L)
DOI: 10.3389/fimmu.2015.00225
PMC: PMC4437037
OpenAlex: W1553047467
Cited by: 315
References: 97
Citations by year: 2026: 18 · 2025: 24 · 2024: 31 · 2023: 38 · 2022: 25 · 2021: 48 · 2020: 36 · 2019: 27 · 2018: 23 · 2017: 24 · 2016: 17 · 2015: 4
FWCI: 2.13
Type: journal article
Language: en
Open access: gold
dx.doi.org
Licence: cc-by
Locations: Frontiers in Immunology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo (13/16010-5, 13/07140-2)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Conselho Nacional de Desenvolvimento Científico e Tecnológico (2013/07140-2)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: peritoneal macrophages, macrophage heterogeneity, macrophage development, macrophage origin, inflammatory monocytes, MHC class II expression, F4/80, transcriptional regulation, IgA production, gut-associated lymphoid tissue, retinoic acid, infection, inflammation, tissue homeostasis

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Revisiting Mouse Peritoneal Macrophages: Heterogeneity, Development, and Function

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