Cyclophosphamide prevents systemic keratinocyte growth factor-induced up-regulation of surfactant protein A after allogeneic transplant in mice.
Cyclophosphamide prevents systemic keratinocyte growth factor-induced up-regulation of surfactant protein A after allogeneic transplant in mice.
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DOI：
10.1164/ajrccm.162.5.2002053
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发表时间：
2000
影响因子：
24.7
通讯作者：
Shuxia Yang;A. Panoskaltsis‐Mortari;D. Ingbar;S. Matalon;Sha Zhu;E. Resnik;C. Farrell;D. Lacey;B. Blazar;I. Y. Haddad
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文献类型：
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作者：
Shuxia Yang;A. Panoskaltsis‐Mortari;D. Ingbar;S. Matalon;Sha Zhu;E. Resnik;C. Farrell;D. Lacey;B. Blazar;I. Y. Haddad
我们报道，骨髓移植（BMT）前给予全身角质形成细胞生长因子（KGF）可预防 BMT 后第 7 天评估的同种异体 T 细胞依赖性肺部炎症，但在注射 T 细胞和环磷酰胺（Cy）调理方案的小鼠中，KGF 的抗炎作用受损。已知气管内 KGF 可刺激表面活性蛋白 A (SP-A) 的表达，这是一种由 II 型肺泡细胞产生的氧化剂敏感 T 细胞免疫调节剂。我们假设同种异体 BMT 后全身 KGF 上调 SP-A，并且 Cy 的添加可能会干扰 KGF 增强 SP-A 产生的能力。在 BMT 后第 7 天测量的同种异体 T 细胞受体照射小鼠中，皮下施用重组人 KGF（BMT 前第 -6、-5 和 -4 天为 5 mg/kg）增加了 SP-A 蛋白和 mRNA。相比之下，在给予 T 细胞和 Cy 的受辐射小鼠中进行相同的 KGF 治疗未能上调 SP-A mRNA 和蛋白质表达。在旨在模拟体内模型的混合淋巴细胞反应实验中，向同种异体激活的 T 细胞中添加人 SP-A（5-50 微克）以剂量依赖性方式抑制白细胞介素 2 的产生。我们得出的结论是，在同种异体 T 细胞受体中 BMT 前全身注射 KGF 上调 SP-A，这可能有助于 KGF 的早期抗炎作用。在给予同种反应性 T 细胞加 Cy 的小鼠中，保护性 KGF 介导的 SP-A 产生被消除。
We reported that systemic keratinocyte growth factor (KGF) given before bone marrow transplantation (BMT) prevents allogeneic T cell-dependent lung inflammation assessed on Day 7 post-BMT, but the antiinflammatory effects of KGF were impaired in mice injected with both T cells and conditioning regimen of cyclophosphamide (Cy). Intratracheal KGF is known to stimulate the expression of surfactant protein A (SP-A), an oxidant-sensitive T cell immunomodulator produced by alveolar type II cells. We hypothesized that systemic KGF up-regulates SP-A after allogeneic BMT, and the addition of Cy may interfere with the ability of KGF to enhance SP-A production. The subcutaneous administration of recombinant human KGF (5 mg/kg on Days -6, -5, and -4 pre-BMT) increased SP-A protein and mRNA in allogeneic T cell-recipient irradiated mice measured on Day 7 post-BMT. In contrast, the same KGF treatment in irradiated mice given T cells and Cy failed to up-regulate SP-A mRNA and protein expression. In mixed lymphocyte reaction experiments designed to simulate the in vivo model, the addition of human SP-A (5-50 microg) to alloactivated T cells suppressed the production of interleukin-2 in a dose-dependent fashion. We conclude that the systemic pre-BMT injection of KGF in recipients of allogeneic T cells up-regulates SP-A, which may contribute to the early antiinflammatory effects of KGF. The protective KGF-mediated SP-A production is abolished in mice given alloreactive T cells plus Cy.