Mouse bone marrow contains large numbers of functionally competent neutrophils
Mouse bone marrow contains large numbers of functionally competent neutrophils
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DOI：
10.1189/jlb.0703340
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发表时间：
2004-04-01
影响因子：
5.5
通讯作者：
Nüsse, O
中科院分区：
文献类型：
--
作者：
Boxio, R;Bossenmeyer-Pourié, C;Nüsse, O
小鼠已成为包括先天免疫在内的免疫学研究的重要模型。创造转基因小鼠为研究基因功能关系提供了独特的可能性。然而，对野生型小鼠中性粒细胞的生理学知之甚少。它们的行为是否像人类中性粒细胞，或者在将结果从小鼠外推到人类时需要考虑物种特异性差异？我们如何从老鼠身上分离出中性粒细胞？由于实际原因，许多关于小鼠中性粒细胞的研究是用骨髓细胞进行的。然而，人骨髓嗜中性粒细胞似乎是异质的，功能不成熟。我们已经分离和比较了中性粒细胞从小鼠骨髓和外周血获得尾部出血。使用相同的Percoll密度梯度，我们从骨髓和血液中获得了形态成熟的中性粒细胞。这两个细胞群体响应甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLF）与初级和次级grannie释放和超氧化物的生产。我们的数据的定量分析揭示了骨髓和血液细胞之间的微小差异。在较低的fMLF浓度刺激血液中性粒细胞的超氧化物产生和初级颗粒释放。然而，最大反应的幅度和动力学相似。主要的区别是两个细胞群的寿命。骨髓细胞在培养物中存活的时间明显更长，这可能表明它们正在接受血液中缺乏的抗炎症信号。我们的数据表明，小鼠骨髓中有大量功能正常的中性粒细胞。感染期间可能需要这个储存器来快速替换循环中的中性粒细胞。
The mouse has become an important model for immunological studies including innate immunity. Creating transgenic mice offers unique possibilities to study gene-function relationships. However, relatively little is known about the physiology of neutrophils from wild-type mice. Do they behave like human neutrophils, or are there species-specific differences that need to be considered when extrapolating results from mice to humans? How do we isolate neutrophils from mice? For practical reasons, many studies on mouse neutrophils are done with bone marrow cells. However, human bone marrow neutrophils appear to be heterogeneous and functionally immature. We have isolated and compared neutrophils from mouse bone marrow and from peripheral blood obtained by tail bleeding. Using the same Percoll((R)) density gradient for both preparations, we have obtained morphologically mature neutrophils from bone marrow and blood. Both cell populations responded to formylmethionyl-leucyl-phenylalanine (fMLF) with primary and secondary grannie release and superoxide production. Quantitative analysis of our data revealed minor differences between cells from bone marrow and blood. Superoxide production and primary granule release were stimulated at lower fMLF concentrations in blood neutrophils. However, the amplitude and the kinetics of maximal responses were similar. The principal difference was the lifespan of the two cell populations. Bone marrow cells survived significantly longer in culture, which may suggest that they are receiving antiapoptic signals that are absent in the blood. Our data suggest that mice have a large reservoir of functionally competent neutrophils in their bone marrow. This reservoir may be needed to replace circulating neutrophits rapidly during infection.