Cited by 103Lipid metabolism and biosynthesisImmune Response and InflammationSphingolipid Metabolism and Signaling

Monocyte Chemoattractant Protein-1/CC Chemokine Ligand 2 Controls Microtubule-Driven Biogenesis and Leukotriene B4-Synthesizing Function of Macrophage Lipid Bodies Elicited by Innate Immune Response

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Pacheco, Patricia, Vieira-de-Abreu, Adriana, Gomes, Rachel N, Barbosa-Lima, Giselle, Wermelinger, Leticia B, Maya-Monteiro, Clarissa M, Silva, Adriana R, Bozza, Marcelo T +3 more·2007·The Journal of Immunology

Abstract

Lipid bodies (also known as lipid droplets) are emerging as inflammatory organelles with roles in the innate immune response to infections and inflammatory processes. In this study, we identified MCP-1 as a key endogenous mediator of lipid body biogenesis in infection-driven inflammatory disorders and we described the cellular mechanisms and signaling pathways involved in the ability of MCP-1 to regulate the biogenesis and leukotriene B4 (LTB4) synthetic function of lipid bodies. In vivo assays in MCP-1−/− mice revealed that endogenous MCP-1 produced during polymicrobial infection or LPS-driven inflammatory responses has a critical role on the activation of lipid body-assembling machinery, as well as on empowering enzymatically these newly formed lipid bodies with LTB4 synthetic function within macrophages. MCP-1 triggered directly the rapid biogenesis of distinctive LTB4-synthesizing lipid bodies via CCR2-driven ERK- and PI3K-dependent intracellular signaling in in vitro-stimulated macrophages. Disturbance of microtubule organization by microtubule-active drugs demonstrated that MCP-1-induced lipid body biogenesis also signals through a pathway dependent on microtubular dynamics. Besides biogenic process, microtubules control LTB4-synthesizing function of MCP-1-elicited lipid bodies, in part by regulating the compartmentalization of key proteins, as adipose differentiation-related protein and 5-lipoxygenase. Therefore, infection-elicited MCP-1, besides its known CCR2-driven chemotactic function, appears as a key activator of lipid body biogenic and functional machineries, signaling through a microtubule-dependent manner.

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Crossref · 10.4049/jimmunol.179.12.8500

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  • PI3 kinase inhibition is a known modulator of lipid droplets in mouse macrophages, but this has not been previously shown in human microglia.

    “PI3 kinase inhibition is a known modulator of LDs in mouse macrophages26 but this has not been previously shown in human microglia.”
  • CCL2 influences lipid droplet biosynthesis and pro-inflammatory polarization, and can interact with other inflammatory mediators.

    “CCL2 has been shown to influence LD biosynthesis [71] and pro-inflammatory polarization, and can interact with other inflammatory mediators [72].”

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Authors
Pacheco, P., Vieira-de-Abreu, A., Gomes, R. N., Barbosa-Lima, G., Wermelinger, L. B., Maya-Monteiro, C. M., Silva, A. R., Bozza, M. T., Castro-Faria-Neto, H. C., Bandeira-Melo, C., & Bozza, P. T.
Affiliations
  • Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz , Rio de Janeiro ,
  • Instituto Oswaldo Cruz (BR)
  • Universidade Federal do Rio de Janeiro (BR)
  • Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,
Venue
The Journal of Immunology
Published
2007-12
Volume
179
Issue
12
Pages
8500-8508
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2158314747
Cited by
103
References
46
Citations by year
2026: 2 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 10
FWCI
4.32
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders
  • Fundação Oswaldo Cruz
  • Universidade Federal do Rio de Janeiro
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords
MCP-1, lipid droplets, leukotriene B4 synthesis, microtubules, CCR2, ERK signaling, PI3K signaling, 5-lipoxygenase, ADRP, co-infection, lipopolysaccharide, innate immunity
MeSH terms
Animals, Chemotaxis, Immunity, Innate, Leukotriene B4, Ligands, Lipopolysaccharides, Macrophages, Mice, Inbred Strains, Microtubules, Sepsis, Chemokine CCL2, Endotoxemia, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase 1, Lipid Metabolism, Mice, Receptors, CCR2

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