Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Ann Surg. 2010 Jan;251(1):120-6. doi: 10.1097/SLA.0b013e3181bfda1c.
To delineate the role of T-helper 2 (Th2) cytokines in the induction of trauma induced myeloid suppressor cells (TIMSC) and the regulation of nitric oxide production.
Trauma induces myeloid cells that express CD11b+/Gr1+ and arginase 1 and exhibit an immune suppressing activity. This article explores the mechanisms that induce TIMSC and the effects on nitric oxide production in response to endotoxin.
TIMSC were studied in response to Th2 cytokines and a subsequent challenge to endotoxin. The role of Th2 cytokines was studied in STAT6-/- mice. Accumulation of TIMSC in spleens was studied using flow cytometry and immunhistochemistry. Plasma was recovered to measure accumulation of nitric oxide metabolites.
TIMSC accumulated in the spleen of injured mice and were particularly sensitive to IL-4 and IL-13 with large inductions of arginase activity. Significant blunting in both the accumulation of TIMSC in the spleen and induction of arginase 1 was observed in STAT6-/- mice after physical injury. Accumulation of nitric oxide metabolites to endotoxin was observed in STAT6-/- mice.
This study shows that induction of CD11b+/Gr1+ cells after physical injury play an essential role in the regulation of nitric oxide production after a septic challenge. The accumulation and induction of arginase 1 in TIMSC is Th2 cytokine dependent. To our knowledge, the role of TIMSC in the regulation of nitric oxide is a novel finding. This observation adds to the possibility that TIMSC could play an important role in immunosuppression observed after physical injury.
描述辅助性 T 细胞 2（Th2）细胞因子在诱导创伤诱导髓系抑制细胞（TIMSC）和调节一氧化氮产生中的作用。
创伤诱导表达 CD11b+/Gr1+和精氨酸酶 1 并具有免疫抑制活性的髓系细胞。本文探讨了诱导 TIMSC 的机制以及对内毒素反应中一氧化氮产生的影响。
研究了 Th2 细胞因子对 TIMSC 的反应以及随后对内毒素的反应。在 STAT6-/-小鼠中研究了 Th2 细胞因子的作用。使用流式细胞术和免疫组织化学研究 TIMSC 在脾脏中的积累。回收血浆以测量一氧化氮代谢物的积累。
TIMSC 在受伤小鼠的脾脏中积累，对 IL-4 和 IL-13 特别敏感，精氨酸酶活性大量诱导。在物理损伤后，STAT6-/-小鼠中观察到 TIMSC 在脾脏中的积累和精氨酸酶 1 的诱导明显减弱。在 STAT6-/-小鼠中观察到内毒素引起的一氧化氮代谢物的积累。
本研究表明，物理损伤后 CD11b+/Gr1+细胞的诱导在脓毒症挑战后一氧化氮产生的调节中起重要作用。TIMSC 中精氨酸酶 1 的积累和诱导依赖于 Th2 细胞因子。据我们所知，TIMSC 在调节一氧化氮中的作用是一个新发现。这一观察结果增加了 TIMSC 可能在物理损伤后观察到的免疫抑制中发挥重要作用的可能性。
