HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pacheco, P. Articles by Bozza, P. T. Search for Related Content PubMed PubMed Citation Articles by Pacheco, P. Articles by Bozza, P. T. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Sepsis

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 Response¹

Patricia Pacheco^*, Adriana Vieira-de-Abreu^*, Rachel N. Gomes^*, Giselle Barbosa-Lima^*, Leticia B. Wermelinger^*, Clarissa M. Maya-Monteiro^*, Adriana R. Silva^*, Marcelo T. Bozza, Hugo C. Castro-Faria-Neto^*, Christianne Bandeira-Melo^2, and Patricia T. Bozza^2,*

^* Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Howard Hughes Medical Institute (to P.T.B.), PRONEX-MCT, Conselho Nacional de Pesquisa (Brazil), and Fundação de Amparo à Pesquisa do Rio de Janeiro.

² Address correspondence and reprint requests to Dr. Patricia T. Bozza, Laboratório de Imunofarmacologia, Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Avenuda Brasil 4365, Manguinhos, Rio de Janeiro, RJ, Brazil 21045-900. E-mail address: pbozza{at}ioc.fiocruz.br or Dr. Christianne Bandeira-Melo, Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil 21941-902. E-mail address: cbmelo{at}biof.ufrj.br

³ Abbreviations used in this paper: ER, endoplasmic reticulum; ADRP, adipose differentiation related protein; LDL, low-density lipoprotein; oxLDL, oxidized LDL; 5-LO, 5-lipoxygenase; LTB₄, leukotriene B₄; CLP, cecum ligation and puncture; EDAC, 1-ethyl-3 (3-dimethylamino-propyl) carbodiimide.

Related articles in The JI:

IN THIS ISSUE

The JI 2007 179: 7991-7992. [Full Text]  

This article has been cited by other articles:

				P. E. Almeida, A. R. Silva, C. M. Maya-Monteiro, D. Torocsik, H. D'Avila, B. Dezso, K. G. Magalhaes, H. C. Castro-Faria-Neto, L. Nagy, and P. T. Bozza Mycobacterium bovis Bacillus Calmette-Guerin Infection Induces TLR2-Dependent Peroxisome Proliferator-Activated Receptor {gamma} Expression and Activation: Functions in Inflammation, Lipid Metabolism, and Pathogenesis J. Immunol., July 15, 2009; 183(2): 1337 - 1345. [Abstract] [Full Text] [PDF]

				C. A. Sorgi, A. Secatto, C. Fontanari, W. M. Turato, C. Belanger, A. I. de Medeiros, S. Kashima, S. Marleau, D. T. Covas, P. T. Bozza, et al. Histoplasma capsulatum Cell Wall {beta}-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B4 Generation and Role in HIV-1 Infection J. Immunol., April 1, 2009; 182(7): 4025 - 4035. [Abstract] [Full Text] [PDF]

				Y. Ye, Y. Lin, J. R. Perez-Polo, B. F. Uretsky, Z. Ye, B. C. Tieu, and Y. Birnbaum Phosphorylation of 5-Lipoxygenase at Ser523 by Protein Kinase A Determines Whether Pioglitazone and Atorvastatin Induce Proinflammatory Leukotriene B4 or Anti-Inflammatory 15-Epi-Lipoxin A4 Production J. Immunol., September 1, 2008; 181(5): 3515 - 3523. [Abstract] [Full Text] [PDF]