Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection

被引:59
作者
Gregory, Alyssa D.
Hogue, Lisa A.
Ferkol, Thomas W.
Link, Daniel C.
机构
[1] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
关键词
D O I
10.1182/blood-2005-01-015081
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Granulocyte colony-stimulating factor (G-CSF) regulates the production, maturation, and function of neutrophils. Its expression is often induced during infection, resulting in high concentrations of G-CSF in inflammatory exudates and in the blood, suggesting that it may regulate both local and systemic neutrophil responses. Herein, we characterize the neutrophil response in G-CSFR-/- mice following intratracheal injection with Pseudomonas aeruginosa-laden agarose beads, modeling the pulmonary infection observed in many patients with cystic fibrosis. G-CSFR-/- mice are markedly susceptible to bronchopulmonary P aeruginosa infection, exhibiting decreased survival and bacterial clearance as well as extensive damage to lung tissue. The systemic neutrophil response was mediated primarily by enhanced neutrophil release from the bone marrow rather than increased neutrophil production and was attenuated in G-CSFR-/- mice. Despite normal to increased local production of inflammatory chemokines, neutrophil accumulation into the infected lung of G-CSFR-/- mice was markedly reduced. Moreover, the percentage of apoptotic neutrophils in the lung was elevated, suggesting that G-CSF signals may play an important role in regulating neutrophil survival at the inflammatory site. Collectively, these data provide new evidence that G-CSIF signals play important but specific roles in the regulation of the systemic and local neutrophil response following infection.
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收藏
页码:3235 / 3243
页数:9
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