¦Â-Adrenergic receptor mediated increases in activation and function of natural killer cells following repeated social disruption

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• 作者：Andrew J. Tarr ; Nicole D. Powell ; Brenda F. Reader ; Neela S. Bhave ; Am ; a L. Roloson ; William E. Carson 3rd ; John F. Sheridan
• 关键词：NK cells ; Inhibitory ; Activation ; Degranulation ; Social disruption ; Stress ; Interferon gamma
• 刊名：Brain, Behavior, and Immunity
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：26
• 期：8
• 页码：1226-1238
• 全文大小：964 K

文摘

Natural killer (NK) cells are specialized innate lymphocytes important in the early defense against tumor and virus bearing cells. Many factors influence the immune system¡¯s effectiveness against pathogens, including stress. Social disruption (SDR) ¡°primes¡± macrophages/monocytes and dendritic cells thereby enhancing their anti-microbial function. What remains unclear is whether similar responses are evident in NK cells. Current studies investigated the cellular distribution and activation/inhibitory phenotypes of NK cells in the spleen, lung, and blood of C57BL/6 male mice following SDR. Furthermore, cytolytic activity and anti-viral cytokine production of splenic NK cells were determined. Lastly, ¦Â-adrenergic receptor (¦Â-AR) signaling was investigated to determine possible mechanisms behind the SDR-induced NK cell alterations. Results indicated NK cells from SDR mice have increased expression of CD16 and CD69 and reduced NKG2a and Ly49a expression on splenic CD3?/DX5+ NK cells indicative of an activated phenotype, both immediately and 14 h post-SDR. Administration of propranolol (10 mg/kg; non-selective ¦Â-adrenergic receptor antagonist) was shown to block these ¡°priming¡± effects at the 14 h time-point. In the lung, SDR had similar effects on activation and inhibitory receptors 14 h post-SDR, however no alterations were evident in the blood besides increased NK cells directly after SDR. Additionally, splenic NK cells from SDR mice had increased CD107a surface expression, cytolytic activity, and IFN-¦Ã production was increased upon costimulation with IgG and IL-2 ex vivo. Collectively, these data suggest that social stress ¡°primes¡± NK cells in the spleen and lung to be more proficient in their cytolytic and anti-viral/tumor effecter functions through ¦Â-adrenergic receptor dependent signaling.