Nishinakamura R, Wiler R, Dirksen U, Morikawa Y, Arai K, Miyajima A, Burdach S, Murray R
DNAX Research Institute, Palo Alto, California 94304, USA.
J Exp Med. 1996 Jun 1;183(6):2657-62. doi: 10.1084/jem.183.6.2657.
Mice mutant for granulocyte macrophage colony-stimulating factor (GM-CSF) or the common receptor component (beta c) for GM-CSF, interleukin (IL)-3, and IL-5 exhibit a lung disorder similar to human pulmonary alveolar proteinosis, a rare disease with congenital, infantile, and adult forms. Bone marrow transplantation and hematopoietic reconstitution of beta c mutant mice with wild-type bone marrow reversed the established disease state in the lungs, defining this disease as hematopoietic in nature. It is likely that the disease involves alveolar macrophages, as donor myeloid cell engraftment into the lungs of mutant recipient mice correlated with reverting both the disease and an abnormal macrophage morphology seen in the lungs of affected animals. Recombination Activating Gene-2 mutant donor bone marrow, which lacks the potential to develop lymphocytes, reversed the pathology in the lungs to the same extent as whole bone marrow. These data establish that certain lung disorders, if of cell-autonomous hematopoietic origin, can be manipulated by bone marrow transplantation.
粒细胞巨噬细胞集落刺激因子（GM-CSF）或GM-CSF、白细胞介素（IL）-3和IL-5的共同受体成分（βc）发生突变的小鼠，会出现一种类似于人类肺泡蛋白沉积症的肺部疾病，这是一种具有先天性、婴儿型和成人型的罕见疾病。用野生型骨髓对βc突变小鼠进行骨髓移植和造血重建，逆转了肺部已确立的疾病状态，从而确定这种疾病本质上是造血系统疾病。这种疾病很可能涉及肺泡巨噬细胞，因为供体髓样细胞植入突变受体小鼠的肺部，与疾病的逆转以及在患病动物肺部观察到的异常巨噬细胞形态的恢复相关。缺乏发育成淋巴细胞潜力的重组激活基因-2突变供体骨髓，在逆转肺部病理方面与全骨髓的效果相同。这些数据表明，某些起源于细胞自主造血的肺部疾病，可以通过骨髓移植来进行调控。
