Adipose tissue macrophages in non-rodent mammals: a comparative study

The stromal vascular fraction (SVF) of adipose tissue in rodents and primates contains mesenchymal stem cells and immune cells. SVF cells have complex metabolic, immune and endocrine functions with biomedical impact. However, in other mammals, the amount of data on SVF stem cells is negligible and whether the SVF hosts immune cells is unknown. In this study, we show that the SVF is rich in immune cells, with a dominance of adipose tissue macrophages (ATMs) in cattle (Bos primigenius taurus), domestic goat (Capra aegagrus hircus), domestic sheep (Ovis aries), domestic cat (Felis catus) and domestic dog (Canis familiaris). ATMs of these species are granulated lysosome-rich cells with lamellipodial protrusions and express the lysosome markers acid phosphatase 5 (ACP-5) and Mac-3/Lamp-2. Using ACP-5 and Mac-3/Lamp-2 as markers, we additionally detected ATMs in other species, such as the domestic horse (Equus ferus caballus), wild boar (Sus scrofa) and red fox (Vulpes vulpes). Feline and canine ATMs also express the murine macrophage marker F4/80 antigen. In the lean condition, the alternative macrophage activation marker CD206 is expressed by feline and canine ATMs and arginase-1 by feline ATMs. Obesity is associated with interleukin-6 and interferon gamma expression and with overt tyrosine nitration in both feline and canine ATMs. This resembles the obesity-induced phenotype switch of murine and human ATMs. Thus, we show, for the first time, that the presence of ATMs is a general trait of mammals. The interaction between the adipose cells and SVF immune cells might be evolutionarily conserved among mammals.University of Ul

Understanding adipose tissue macrophage self-renewal: mechanisms involving liver X receptors

The regulation of macrophage homeostasis is relevant in health and in the development of diseases. As metabolically relevant immune cells of the adipose tissue (AT), adipose tissue macrophages (ATMs) contribute to AT inflammation, which is dependant on the number and the activation state of ATMs. Herein, ATM homeostasis of white AT depots from lean adult mice was shown to be maintained by yolk sac-derived macrophages through their ability to undergo cell division to self-renew. However, blood monocytes also contributed to the maintenance of ATM homeostasis after bone marrow transplantation. Furthermore, ATM self-renewal was shown to be influenced by endocrine signals. The endocrine disruptor bisphenol A (BPA), which preferably bioaccumulates in the AT, increased macrophage self-renewal and mildly affected their activation states, without affecting their function in vitro. This increase in self-renewal was associated with increased phosphorylation of extracellular signal-regulated kinase and a slight increase in liver X receptor alpha (LXRα) expression, whose inhibition induced, whereas its activation impeded macrophage self-renewal. In addition, self-renewing (Ki67+) macrophages expressed lower LXRα levels than quiescent (Ki67-) macrophages. Correspondingly, tissue-resident macrophage pools with increased Ki67- macrophages had elevated LXRα expression levels and Ki67+ macrophages decreased LXRα expression. Moreover, LXR signaling modulated the self-renewal of classically activated (M1) and alternatively activated (M2) macrophages by either reducing or increasing the number of macrophages in vitro, respectively. Over all, these data show that BPA unconsciously released into the environment can impede ATM homeostais, whereas LXRα signaling may protect from uncontrolled macrophage expansion, which is associated with the onset of obesity and its associated metabolic syndrome

MOESM1 of Three-dimensional tumor spheroids for in vitro analysis of bacteria as gene delivery vectors in tumor therapy

Additional file 1: Figure S1. Characterisation of HT-29 MCTS