Jorgensen Lars N, Agren Magnus S, Madsen Søren M, Kallehave Finn, Vossoughi Faranak, Rasmussen Annette, Gottrup Finn
Copenhagen Wound Healing Center and the Department of Surgical Gastroenterology, Sundby Hospital, University of Copenhagen, Copenhagen, Denmark.
Ann Surg. 2002 Nov;236(5):684-92. doi: 10.1097/00000658-200211000-00020.
The authors studied the dose-dependent effect of topically administered granulocyte-macrophage colony-stimulating factor (GM-CSF) on the connective tissue response using an experimental repair model in surgical patients.
GM-CSF is primarily indicated in the treatment of immunosuppressed states. The effect of GM-CSF on the tissue repair response in humans is unclear.
Expanded polytetrafluoroethylene tubes were implanted subcutaneously and GM-CSF was applied locally at concentrations of 0.1 micro g/mL (total dose 0.4 micro g), 1.0 micro g/mL (4.0 micro g), 10 micro g/mL (40 micro g), or 75 micro g/mL (300 micro g) in one arm and saline alone (control) in the contralateral arm of 56 surgical patients. The content of collagen and total protein in the tubes was quantified as hydroxyproline and proline by high-performance liquid chromatography 10 days after implantation. Cellularity and the number of procollagen I-positive fibroblasts were determined by histology and immunohistochemistry. The direct effects of GM-CSF on collagen production by and proliferation of wound fibroblasts cultured from granulation tissue were also measured.
Local application of GM-CSF stimulated the inflammatory cell infiltration but reduced the number of fibroblasts in the granulation tissue. GM-CSF treatment suppressed specifically and dose-dependently collagen deposition by up to 81%. A reduced collagen accumulation was also found in the control-treated arm at GM-CSF doses of 4 micro g or more, indicating a systemic depressive effect of GM-CSF on tissue repair. The selective downregulation of collagen production by GM-CSF was also found in wound fibroblasts in vitro.
Inhibition of fibrogenesis with GM-CSF intervention may impair tissue repair processes during surgery.
作者使用手术患者的实验性修复模型，研究局部应用粒细胞巨噬细胞集落刺激因子（GM-CSF）对结缔组织反应的剂量依赖性效应。
GM-CSF主要用于治疗免疫抑制状态。GM-CSF对人体组织修复反应的影响尚不清楚。
将膨体聚四氟乙烯管皮下植入56例手术患者体内，在一侧手臂局部应用浓度为0.1μg/mL（总剂量0.4μg）、1.0μg/mL（4.0μg）、10μg/mL（40μg）或75μg/mL（300μg）的GM-CSF，对侧手臂仅应用生理盐水（对照）。植入10天后，通过高效液相色谱法将管内胶原蛋白和总蛋白的含量定量为羟脯氨酸和脯氨酸。通过组织学和免疫组织化学测定细胞数量和I型前胶原阳性成纤维细胞的数量。还测量了GM-CSF对从肉芽组织培养的伤口成纤维细胞产生胶原蛋白和增殖的直接影响。
局部应用GM-CSF刺激炎症细胞浸润，但减少了肉芽组织中的成纤维细胞数量。GM-CSF治疗特异性地且剂量依赖性地抑制胶原蛋白沉积高达81%。在GM-CSF剂量为4μg或更高时，对照治疗组的手臂中也发现胶原蛋白积累减少，表明GM-CSF对组织修复有全身抑制作用。在体外伤口成纤维细胞中也发现GM-CSF对胶原蛋白产生有选择性下调作用。
GM-CSF干预抑制纤维生成可能会损害手术期间的组织修复过程。
