Inman M D, Denburg J A, Ellis R, Dahlback M, O'Byrne P M
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
Am J Respir Cell Mol Biol. 1996 Sep;15(3):305-11. doi: 10.1165/ajrcmb.15.3.8924277.
We have previously reported that bone marrow progenitors in dogs, specifically granulocyte-macrophage colony-forming units (GM-CFU), increase developing airway hyperresponsiveness after inhalation of the allergen Ascaris suum. In the present study, we evaluated whether this increased marrow hemopoietic activity can be stimulated by a factor in serum after allergen challenge. Serum samples taken from dogs prior to and 20 min, 2 h, and 24 h after Ascaris or diluent challenge were added to bone marrow cells aspirated prior to challenge, and GM-CFU measured. A second bone marrow aspirate was performed 24 h after challenge. Nonadherent mononuclear bone marrow cells were incubated for 8 days in the presence of the serum and recombinant canine hemopoietic cytokines (stem cell factor, granulocyte colony-stimulating factor, GM colony-stimulating factor). Eight dogs that developed (airway responders) and eight dogs that did not develop (airway nonresponders) allergen-induced airway hyperresponsiveness were studied. Allergen inhalation increased bone marrow GM-CFU in response to all three growth media in vitro for the airway responder (P < 0.05) but not airway nonresponder dogs. The 24-h serum, taken from the airway responder but not the airway nonresponder dogs, produced a similar increase in granulocyte progenitors when added to the bone marrow taken before allergen inhalation (P < 0.05). These findings demonstrate that bone marrow-derived granulocyte progenitors are upregulated by a factor that can be shown to be present in serum 24 h after allergen challenge in dogs that develop allergen-induced airway hyperresponsiveness. Whether in vivo stimulation of bone marrow inflammatory cell production is necessary for the development of allergen-induced airway hyperresponsiveness remains to be proven.
我们之前曾报道，犬类的骨髓祖细胞，特别是粒细胞-巨噬细胞集落形成单位（GM-CFU），在吸入过敏原猪蛔虫后会增加气道高反应性的发展。在本研究中，我们评估了这种增加的骨髓造血活性是否能被过敏原激发后血清中的一种因子所刺激。将在猪蛔虫或稀释剂激发前、激发后20分钟、2小时和24小时采集的犬血清样本，添加到激发前抽取的骨髓细胞中，并测量GM-CFU。激发后24小时进行第二次骨髓穿刺。非贴壁单核骨髓细胞在血清和重组犬造血细胞因子（干细胞因子、粒细胞集落刺激因子、GM集落刺激因子）存在的情况下孵育8天。研究了8只出现（气道反应者）和8只未出现（气道无反应者）过敏原诱导气道高反应性的犬。过敏原吸入使气道反应者的骨髓GM-CFU在体外对所有三种生长培养基均有反应性增加（P < 0.05），但气道无反应者的犬则无此现象。从气道反应者而非气道无反应者的犬采集的24小时血清，在添加到过敏原吸入前采集的骨髓中时，粒细胞祖细胞产生了类似的增加（P < 0.05）。这些发现表明，在出现过敏原诱导气道高反应性的犬中，骨髓来源的粒细胞祖细胞会被一种在过敏原激发后24小时血清中可检测到的因子上调。体内刺激骨髓炎性细胞产生对于过敏原诱导气道高反应性的发展是否必要仍有待证实。
