Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16+, CCR5+and TLR8+monocytes.
Macrophage infiltration into adipose tissue (AT) is a hallmark of the chronic inflammatory response in obesity and is supported by an intense monocyte migration towards AT. Although it has been detected an increased proportion of circulating CD16+monocyte subsets in obese subjects, the mechanisms underlying this effect and the contribution of these cells to the inflamed profile of obese AT are still poorly understood. We investigated whether factors secreted by human obese omental AT could polarize monocytes to CD16+enriched phenotype, and how these changes could modify their migratory capacity towards adipose tissue itself. We show that explants of human obese omental AT, obtained during bariatric surgery, released higher levels of MIP1-α, TNFα, leptin and also VEGF, together with increasing amounts of microparticles (MP), when compared to explants of lean subcutaneous AT. A higher content of circulating MP derived from preadipocytes and leukocytes was also detected in plasma of obese subjects. Conditioned media or MP released from obese omental AT increased CD16 and CCR5 expression on CD14+CD16-monocytes and augmented their migratory capacity towards the conditioned media from obese omental AT, itself. This effect was inhibited when MIP1-α was neutralized. Additionally, we demonstrate that MP derived from obese omental AT carry and transfer TLR8 to monocytes, thus triggering an increase in CD16 expression in those cells. Our data shows a positive feedback loop between blood monocytes and obese omental AT, which releases chemotactic mediators and TLR8-enriched MP, thus inducing an up-regulation of CD16+monocytes, favoring leukocyte infiltration in the obese omental AT.
Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Mariana
M
Renovato-Martins
Departamento de Farmacologia Clínica e Básica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
Maria Eline
ME
Matheus
Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Isadora Ramos
IR
de Andrade
Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Departamento de Farmacologia Clínica e Básica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
João Alfredo
JA
Moraes
Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Simone Vargas
SV
da Silva
Departamento de Nutrição Básica e Experimental, Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Brazil.
Marta
M
Citelli Dos Reis
Serviço de Cirurgia Plástica, Departamento de Cirurgia Geral, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil.
Antônio Augusto Peixoto
AA
de Souza
Serviço de Cirurgia Plástica, Departamento de Cirurgia Geral, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil.
César Cláudio
CC
da Silva
Laboratório de Pesquisa Clínica e Experimental em Biologia Vascular, Departamento de Fisiologia, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Eliete
E
Bouskela
Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: barja-fidalgo@uerj.br.
Christina
C
Barja-Fidalgo
D000273:Adipose Tissue / Q000276:immunology* / Q000473:pathology; D000328:Adult; D055252:Cell-Derived Microparticles / Q000276:immunology* / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D009765:Obesity / Q000276:immunology* / Q000473:pathology; D019713:Receptors, CCR5 / Q000032:analysis / Q000276:immunology*; D017452:Receptors, IgG / Q000032:analysis / Q000276:immunology*; D051200:Toll-Like Receptor 8 / Q000032:analysis / Q000276:immunology*
C584933:CCR5 protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D019713:Receptors, CCR5; D017452:Receptors, IgG; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8
CCR5; CD16(+) monocytes; MIP-1α; Obesity; TLR8; adipose tissue