P09 – Palmitate Induces Macrophage Polarization towards M2

Author(s):
Fangming Xiu, Michael Li Diao, Marc Jeschke, Sunnybrook Health Sciences Centre

Background: The hypermetabolic stress response occurs in almost every burn patient with burns over 20 % of their body surface area is associated with severe inflammation and immune dysfunction. As opposed to a chronic low-grade inflammatory state of M1-macrophage (M1MΦ) dominant in metabolic diseases, adipogenesis and accumulation of tissue, M2MΦ are hallmarks of prolonged critical illness. M2MΦ are shown to be predominantly present in humans with severe trauma including burn injuries, sepsis in the peripheral blood and adipose tissues as well as the liver and lungs. Although increased protein levels of PPARγ is a key signal in M2MΦ polarization, it has been found in adipose tissue of critically-ill patients and no study has identified the trigger for the M2 polarization.

Hypothesis: We hypothesize that palmitate with our without glucose will induce a shift towards type 2 macrophages.

Methods: In this study we explored the long-term effects of glucose and Palmitate on macrophage differentiation and function by using ex vivo bone marrow-derived macrophage (BMM) culture. The doses of glucose and Palmitate were 4.5 mM, 7.5mM, 10 mM and 12.5 mM for glucose, and 0.25 mM, 0.5 mM for Palmitate, respectively.

Results: At the end of 7 days culture, we found both glucose and Palmitate decreased the phagocytosis and HLA-DR expression of BMM. What is more interesting is that Palmitate alone or in combination with glucose (10 mM) led to an alternative macrophage polarization (M2MΦ) as defined by increased production of IL-10 and decreased IL-12 and TNF-α.

Conclusions: Our findings are that glucose and Palmitate enhance the macrophage polarization towards M2MΦ suggest that dominant accumulation of M2MΦ in adipose tissues and liver may be resulted from increased concentrations of blood glucose and free fatty acids in critical illness.