Neutrophil mobilization from the bone marrow during polymicrobial sepsis is dependent on CXCL12 signaling.
Neutrophil mobilization from the bone marrow during polymicrobial sepsis is dependent on CXCL12 signaling.
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DOI：
10.4049/jimmunol.1100588
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发表时间：
2011-07-15
期刊：
影响因子：
--
通讯作者：
Efron PA
中科院分区：
文献类型：
--
作者：
Delano MJ;Kelly-Scumpia KM;Thayer TC;Winfield RD;Scumpia PO;Cuenca AG;Harrington PB;O'Malley KA;Warner E;Gabrilovich S;Mathews CE;Laface D;Heyworth PG;Ramphal R;Strieter RM;Moldawer LL;Efron PA
中性粒细胞对于宿主成功根除细菌病原体和存活至多微生物败血症是必不可少的。在炎症期间，骨髓提供大量的中性粒细胞储备，这些中性粒细胞被释放到外周循环中，在外周循环中它们穿过感染部位。虽然中性粒细胞是生存所必需的，但很少有研究调查了多微生物败血症期间中性粒细胞从骨髓动员的机制。使用盲肠结扎和穿孔的多微生物脓毒症模型，我们证明了在脓毒症期间骨髓中的中性粒细胞动员不依赖于TLR 4、MyD 88、TRIF、IFNARα/β或CXCR 2通路信号传导。与此相反，我们观察到，骨髓CXCL 12 mRNA丰度和特定的CXCL 12水平急剧下降，而脾CXCR 4 mRNA和细胞表面表达增加脓毒症。阻断CXCL 12活性通过抑制脓毒症期间粒细胞的骨髓释放而显著减少血液嗜中性粒细胞。然而，CXCL 12抑制对骨髓中性粒细胞前体和造血祖细胞的扩增没有影响。通过CXCL 12阻断的骨髓中性粒细胞保留防止了血液嗜中性粒细胞，抑制了腹膜中性粒细胞积聚，允许显著的腹膜细菌侵入和升高的多微生物败血症死亡率。我们的结论是，在脓毒症过程中的CXCL 12信号模式的变化是必不可少的中性粒细胞骨髓动员和主机的生存，而对骨髓粒细胞生成的影响不大。
Neutrophils are essential for successful host eradication of bacterial pathogens and for survival to polymicrobial sepsis. During inflammation, the bone marrow provides a large reserve of neutrophils that are released into the peripheral circulation where they traverse to sites of infection. Although neutrophils are essential for survival, few studies have investigated the mechanisms responsible for neutrophil mobilization from the bone marrow during polymicrobial sepsis. Using a cecal ligation and puncture model of polymicrobial sepsis, we demonstrate that neutrophil mobilization from the bone marrow is not dependent on TLR4, MyD88, TRIF, IFNARα/β or CXCR2 pathway signaling during sepsis. In contrast, we observe that bone marrow CXCL12 mRNA abundance and specific CXCL12 levels are sharply reduced, while splenic CXCR4 mRNA and cell surface expression are increased during sepsis. Blocking CXCL12 activity significantly reduced the blood neutrophilia by inhibiting bone marrow release of granulocytes during sepsis. CXCL12 inhibition, however, had no impact on the expansion of bone marrow neutrophil precursors and hematopoietic progenitors. Bone marrow neutrophil retention by CXCL12 blockade prevented blood neutrophilia, inhibited peritoneal neutrophil accumulation, allowed significant peritoneal bacterial invasion and elevated polymicrobial sepsis mortality. We conclude that changes in the pattern of CXCL12 signaling during sepsis are essential for neutrophil bone marrow mobilization and host survival while having little impact on bone marrow granulopoiesis.
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影响因子：
56.9
作者：
METCALF, D
通讯作者：
METCALF, D
影响因子：
32.4
作者：
Miller, LS;O'Connell, RM;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
15.9
作者：
Eash, Kyle J.;Greenbaum, Adam M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
DOI：
10.1073/pnas.1031788100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Hotchkiss, RS;Chang, KC;Karl, IE
通讯作者：
Karl, IE
影响因子：
6.2
作者：
DUNN, DL
通讯作者：
DUNN, DL