Ewa Kontny1, Monika Prochorec-Sobieszek. 1. Department of Pathophysiology, Immunology and Pathomorphology, Institute of Rheumatology, Spartańska 1, 02-637 Warsaw, Poland. ewa.kontny@wp.pl.
Abstract
OBJECTIVES: The objectives of this study were to characterize macrophages resident in inflamed articular adipose tissue (AAT) and non-inflamed subcutaneous adipose tissue (ScAT) of RA patients and to evaluate the basal and cytokine-triggered secretory activities of these tissues. METHODS: Tissues were obtained from patients undergoing knee joint replacement surgery. The number of total CD68(+), CD14(+) and CD163(+) macrophages was evaluated by immunohistochemistry. The concentrations of select factors were measured in supernatants from untreated and cytokine-treated tissue explant cultures using ELISA. IL-1β and TNF were applied as the stimuli. RESULTS: Paired samples of AAT and ScAT, obtained from the same patients, contained a similar number of macrophages, displaying an M2-skewed phenotype. Both tissues released equivalent amounts of IL-1β, TNF, IL-10 and macrophage migration inhibitory factor (MIF). However, AAT secreted more chemokines (CCL2, CCL5), cytokines [IL-6, IL-8, IL-1 receptor antagonist (IL-1Ra)], hepatocyte growth factor (HGF) and MMP-3 than ScAT. Basal secretion of adipocytokines was not patient specific. Except for HGF and MIF, cytokine treatment up-regulated the release of these factors from both tissues, but also upon stimulation AAT produced more IL-6, IL-8 and IL-1Ra than ScAT. CONCLUSION: The secretory activity, reflecting cell activation status but not phenotype or the number of macrophages, discriminates rheumatoid AAT from ScAT. By releasing various factors possessing chemotactic, proinflammatory, anti-inflammatory and tissue degrading activities, AAT resident macrophages may drive and control local pathological processes.
OBJECTIVES: The objectives of this study were to characterize macrophages resident in inflamed articular adipose tissue (AAT) and non-inflamed subcutaneous adipose tissue (ScAT) of RApatients and to evaluate the basal and cytokine-triggered secretory activities of these tissues. METHODS: Tissues were obtained from patients undergoing knee joint replacement surgery. The number of total CD68(+), CD14(+) and CD163(+) macrophages was evaluated by immunohistochemistry. The concentrations of select factors were measured in supernatants from untreated and cytokine-treated tissue explant cultures using ELISA. IL-1β and TNF were applied as the stimuli. RESULTS: Paired samples of AAT and ScAT, obtained from the same patients, contained a similar number of macrophages, displaying an M2-skewed phenotype. Both tissues released equivalent amounts of IL-1β, TNF, IL-10 and macrophage migration inhibitory factor (MIF). However, AAT secreted more chemokines (CCL2, CCL5), cytokines [IL-6, IL-8, IL-1 receptor antagonist (IL-1Ra)], hepatocyte growth factor (HGF) and MMP-3 than ScAT. Basal secretion of adipocytokines was not patient specific. Except for HGF and MIF, cytokine treatment up-regulated the release of these factors from both tissues, but also upon stimulation AAT produced more IL-6, IL-8 and IL-1Ra than ScAT. CONCLUSION: The secretory activity, reflecting cell activation status but not phenotype or the number of macrophages, discriminates rheumatoid AAT from ScAT. By releasing various factors possessing chemotactic, proinflammatory, anti-inflammatory and tissue degrading activities, AAT resident macrophages may drive and control local pathological processes.
Authors: Manuel R Schmidli; Bettina Fuhrer; Nadine Kurt; David Senn; Michaela Drögemüller; Ulrich Rytz; David E Spreng; Simone Forterre Journal: BMC Vet Res Date: 2018-05-16 Impact factor: 2.741
Authors: Michael J Ahlers; Brandon D Lowery; Eric Farber-Eger; Thomas J Wang; William Bradham; Michelle J Ormseth; Cecilia P Chung; C Michael Stein; Deepak K Gupta Journal: J Am Heart Assoc Date: 2020-05-07 Impact factor: 5.501