Department of Trauma, University Medical Centre Utrecht, Utrecht, Netherlands.
Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands.
Front Immunol. 2022 May 17;13:883863. doi: 10.3389/fimmu.2022.883863. eCollection 2022.
Extensive trauma surgery evokes an immediate cellular immune response including altered circulatory neutrophil numbers. The concurrent bone marrow (BM) response however is currently unclear. We hypothesize that these BM changes include (1) a relative reduction of the bone marrow neutrophil fraction and (2) increasing heterogeneity of the bone marrow neutrophil pool due to (3) the appearance of aged/returning neutrophils from circulation into the BM-compartment.
Eight pigs were included in a standardized extensive trauma surgery model. Blood and bone marrow samples were collected at baseline and after 3 hours of ongoing trauma surgery. Leukocyte and subtype counts and cell surface receptor expression levels were studied by flow cytometry.
All animals survived the interventions. A significant drop in circulating neutrophil counts from 9.3 to 3.2x10 cells/ml (P=0.001) occurred after intervention, whereas circulatory neutrophil cell surface expression of CD11b increased. The concurrent bone marrow response included an increase of the BM neutrophil fraction from 63 ± 3 to 71 ± 3 percent (P<0.05). Simultaneously, the BM neutrophil pool became increasingly mature with a relative increase of a CXCR4-neutrophil subtype that was virtually absent at baseline.
The current study shows a shift in composition of the BM neutrophil pool during extensive trauma surgery that was associated with a relatively circulatory neutropenia. More specifically, under these conditions BM neutrophils were more mature than under homeostatic conditions and a CXCR4-neutrophil subset became overrepresented possibly reflecting remigration of aged neutrophils to the BM. These findings may contribute to the development of novel interventions aimed to modify the trauma-induced immune response in the BM.
广泛的创伤手术会引发即时的细胞免疫反应，包括循环中性粒细胞数量的改变。然而，目前尚不清楚骨髓（BM）的反应情况。我们假设这些 BM 变化包括：（1）骨髓中性粒细胞比例相对降低，（2）由于（3）循环中的老化/回归中性粒细胞进入 BM 池，骨髓中性粒细胞池的异质性增加。
8 头猪被纳入标准化的广泛创伤手术模型。在基线和持续创伤手术后 3 小时采集血液和骨髓样本。通过流式细胞术研究白细胞和亚型计数以及细胞表面受体表达水平。
所有动物均能耐受干预措施。干预后循环中性粒细胞计数从 9.3 降至 3.2x10 个细胞/ml（P=0.001），而循环中性粒细胞细胞表面 CD11b 的表达增加。同时，骨髓反应包括骨髓中性粒细胞比例从 63±3%增加至 71±3%（P<0.05）。同时，BM 中性粒细胞池变得越来越成熟，具有相对增加的 CXCR4-中性粒细胞亚型，该亚型在基线时几乎不存在。
本研究表明，在广泛的创伤手术过程中，BM 中性粒细胞池的组成发生了变化，这与循环中性粒细胞减少有关。更具体地说，在这些条件下，BM 中性粒细胞比在稳态条件下更成熟，并且 CXCR4-中性粒细胞亚群的代表性增加，可能反映了老化中性粒细胞向 BM 的再迁移。这些发现可能有助于开发旨在改变 BM 中创伤诱导的免疫反应的新干预措施。
