Matute-Bello G, Liles W C, Radella F, Steinberg K P, Ruzinski J T, Hudson L D, Martin T R
Medical Research Service, Seattle VA Medical Center, Division of Pulmonary Medicine, WA, USA.
Crit Care Med. 2000 Jan;28(1):1-7. doi: 10.1097/00003246-200001000-00001.
To determine whether bronchoalveolar lavage fluid (BALF) from patients either at risk for the acute respiratory distress syndrome (ARDS) or with sustained ARDS modulates neutrophil apoptosis; to measure the BALF concentrations of the apoptosis inhibitors granulocyte colony-stimulating factor (G-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) before and after the onset of ARDS; and to determine whether the BALF concentrations of G-CSF and/or GM-CSF are associated with clinical outcome.
Prospective cohort study.
Tertiary university hospital.
Twenty patients at risk for ARDS and 45 patients with established ARDS.
Patients at risk for ARDS underwent bronchoalveolar lavage within 24 hrs of being identified, then again 72 hrs later. Patients with ARDS underwent bronchoalveolar lavage within 24 hrs of meeting ARDS criteria, then again on days 3, 7, and 14 of the disease.
Normal peripheral blood neutrophil were incubated overnight in BALF from normal volunteers, from patients at risk for ARDS, or from patients with ARDS. neutrophil apoptosis was determined by flow cytometric analysis of annexin V binding. G-CSF and GM-CSF were measured in BALF by immunoassays. Compared with normal BALF, BALF from patients on days 1 and 3 of ARDS inhibited neutrophil apoptosis, but BALF from patients at later stages of ARDS, or from patients at risk for ARDS, did not. The BALF concentrations of both G-CSF and GM-CSF were elevated early in ARDS and decreased toward later stages. Patients who lived had significantly higher concentrations of GM-CSF in the BALF than those who died.
We conclude that the antiapoptotic effect of ARDS BALF on normal neutrophil is highest during early ARDS, and decreases during late ARDS. G-CSF and GM-CSF are present in BALF from patients with ARDS, and their concentrations parallel the antiapoptotic effect of ARDS BALF. These data support the concept that the life-span of neutrophil in the air spaces is modulated during acute inflammation. GM-CSF in the air spaces is associated with improved survival in patients with ARDS.
确定急性呼吸窘迫综合征（ARDS）高危患者或持续性ARDS患者的支气管肺泡灌洗液（BALF）是否调节中性粒细胞凋亡；测量ARDS发作前后凋亡抑制因子粒细胞集落刺激因子（G-CSF）和粒细胞/巨噬细胞集落刺激因子（GM-CSF）在BALF中的浓度；并确定G-CSF和/或GM-CSF的BALF浓度是否与临床结局相关。
前瞻性队列研究。
三级大学医院。
20例ARDS高危患者和45例确诊ARDS患者。
ARDS高危患者在被识别后24小时内进行支气管肺泡灌洗，然后在72小时后再次进行灌洗。ARDS患者在符合ARDS标准后24小时内进行支气管肺泡灌洗，然后在疾病的第3、7和14天再次进行灌洗。
将正常外周血中性粒细胞在正常志愿者、ARDS高危患者或ARDS患者的BALF中孵育过夜。通过膜联蛋白V结合的流式细胞术分析确定中性粒细胞凋亡。通过免疫测定法测量BALF中的G-CSF和GM-CSF。与正常BALF相比，ARDS患者第1天和第3天的BALF抑制中性粒细胞凋亡，但ARDS后期患者或ARDS高危患者的BALF则无此作用。ARDS早期G-CSF和GM-CSF的BALF浓度均升高，后期降低。存活患者BALF中GM-CSF的浓度显著高于死亡患者。
我们得出结论，ARDS BALF对正常中性粒细胞的抗凋亡作用在ARDS早期最高，在ARDS后期降低。ARDS患者的BALF中存在G-CSF和GM-CSF，其浓度与ARDS BALF的抗凋亡作用平行。这些数据支持了在急性炎症期间肺泡间隙中性粒细胞寿命受到调节的概念。肺泡间隙中的GM-CSF与ARDS患者生存率提高相关。
