Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112-1393, USA.
Alcohol Clin Exp Res. 2010 Dec;34(12):2035-43. doi: 10.1111/j.1530-0277.2010.01291.x.
Alcohol abuse is associated with an increased incidence and severity of pneumonia. In both the general population and individuals consuming excess alcohol, Streptococcus pneumoniae is the most frequent lung infection pathogen. Alcoholic patients with pneumonia frequently present with granulocytopenia, which is predictive of increased mortality. The mechanisms underlying this impaired granulopoietic response to pneumococcal pneumonia have yet to be elucidated.
Acute alcohol intoxication was induced in mice 30 minutes before intrapulmonary infection with S. pneumoniae. Bone marrow, lung, and blood samples were collected. Bone marrow cells were also isolated from naïve mice and treated in vitro with plasma from mice infected with S. pneumoniae.
Alcohol intoxication impaired the pneumococcal-induced increase in granulocyte recruitment into the alveolar space, decreased bacterial clearance from the lung, and increased mortality. Pneumococcal pneumonia significantly increased bone marrow lineage(-) c-Kit(+) Sca-1(+) (LKS) cell number and colony-forming unit-granulocytes and monocyte (CFU-GM) activity of these cells. Both enhanced proliferation of LKS cells and re-expression of Sca-1 surface protein on downstream progenitor cells bearing lineage(-) c-Kit(+) Sca-1(-) surface markers accounted for the expansion of marrow LSK cells during pneumonia. Alcohol intoxication impaired these 2 mechanisms of LKS cell population expansion and was associated with a relative granulocytopenia during pneumococcal lung infection.
Alcohol inhibits the hematopoietic precursor cell response to pneumonia, which may serve as a mechanism underlying the granulocytopenia and impaired host defense in alcohol abusers with bacterial pneumonia.
酗酒与肺炎发病率和严重程度的增加有关。在普通人群和过量饮酒者中，肺炎链球菌是最常见的肺部感染病原体。患有肺炎的酗酒患者常伴有粒细胞减少症，这预示着死亡率增加。导致这种肺炎球菌性肺炎造血前体细胞反应受损的机制尚未阐明。
在经肺感染肺炎链球菌前 30 分钟，诱导小鼠急性酒精中毒。收集骨髓、肺和血液样本。还从幼稚小鼠中分离骨髓细胞，并在体外用感染肺炎链球菌的小鼠血浆处理。
酒精中毒可损害肺炎链球菌诱导的肺泡空间中性粒细胞募集增加，降低肺部细菌清除率，并增加死亡率。肺炎链球菌感染显著增加骨髓谱系(-)c-Kit(+)Sca-1(+)（LKS）细胞数量和骨髓细胞集落形成单位-粒细胞和单核细胞（CFU-GM）活性。LKS 细胞的增殖增强和下游具有谱系(-)c-Kit(+)Sca-1(-)表面标志物的祖细胞上 Sca-1 表面蛋白的再表达，共同导致肺炎期间骨髓 LSK 细胞的扩增。酒精中毒损害了 LKS 细胞群体扩增的这 2 种机制，并与肺炎链球菌肺部感染期间相对粒细胞减少症有关。
酒精抑制了造血前体细胞对肺炎的反应，这可能是酗酒者细菌性肺炎时粒细胞减少和宿主防御受损的机制之一。
