Broide D H, Smith C M, Wasserman S I
Department of Medicine, University of California, San Diego 92103.
J Immunol. 1990 Sep 15;145(6):1838-44.
As elevated bronchoalveolar lavage (BAL) fluid histamine levels are noted in patients with pulmonary fibrosis (PF), we assayed BAL fluid from 16 patients with PF for the presence of a histamine releasing factor (HRF). HRF activity was assayed by measuring release of the preformed mast cell-derived mediators, histamine, or beta-hexosaminidase (beta-hex) from a purified population of IL-3 dependent mouse bone marrow derived mast cells (MBMMC) or human blood basophils. Mean BAL cell free histamine levels in the patients with PF was 1226 +/- 1349 pg/ml, whereas BAL histamine levels in a comparison group of six non-PF patients was 118 +/- 60 pg/ml. HRF was significantly elevated in BAL fluid of patients with PF (mean beta-hex release 24.5 +/- 12.9%; range 6.8 to 52.4%) compared to the non-PF group of patients (mean beta-hex release 7.9 +/- 7.7%; range 1.8 to 20.7%). The PF HRF not only degranulated MBMMC, but also induced the generation of the arachidonic acid metabolite leukotriene C4 from MBMMC (24.6 +/- 4.2 ng leukotriene C4/10(6) MBMMC). The PF HRF did not appear to be a cytokine previously identified in BAL fluid of patients with PF (i.e., platelet derived growth factor or insulin growth factor-1) or a human cytokine able to degranulate human basophils (i.e., IL-1, or granulocyte-macrophage-CSF) as these recombinant human cytokines did not induce MBMMC beta-hex release. Physicochemical characterization of the HRF revealed that it was relatively heat stable, pronase sensitive and on Sephadex G-75 and G-200 column chromatography had an apparent molecular mass of 30 to 50 kDa. The ability of PF BAL to induce beta-hex release from MBMMC was not dependent on IgE as unsensitized or lactic acid treated MBMMC release similar amounts of beta-hex compared to MBMMC sensitized with IgE. Thus, BAL fluid of patients with PF contains an HRF that induces beta-hex release from MBMMC via an IgE-independent mechanism. The presence of the HRF could explain elevated BAL histamine levels in patients with PF.
由于在肺纤维化（PF）患者中观察到支气管肺泡灌洗（BAL）液组胺水平升高，我们检测了16例PF患者的BAL液中组胺释放因子（HRF）的存在情况。通过测量预先形成的肥大细胞衍生介质、组胺或β-己糖胺酶（β-己）从纯化的依赖白细胞介素-3的小鼠骨髓衍生肥大细胞（MBMMC）或人血嗜碱性粒细胞群体中的释放来检测HRF活性。PF患者的平均BAL无细胞组胺水平为1226±1349 pg/ml，而6例非PF患者的比较组中BAL组胺水平为118±60 pg/ml。与非PF患者组（平均β-己释放7.9±7.7%；范围1.8至20.7%）相比，PF患者BAL液中的HRF显著升高（平均β-己释放24.5±12.9%；范围6.8至52.4%）。PF HRF不仅使MBMMC脱颗粒，还诱导MBMMC产生花生四烯酸代谢产物白三烯C4（24.6±4.2 ng白三烯C4/10⁶ MBMMC）。PF HRF似乎不是先前在PF患者BAL液中鉴定出的细胞因子（即血小板衍生生长因子或胰岛素生长因子-1），也不是能够使人类嗜碱性粒细胞脱颗粒的人类细胞因子（即白细胞介素-1或粒细胞-巨噬细胞集落刺激因子），因为这些重组人类细胞因子不会诱导MBMMC的β-己释放。HRF的物理化学特性表明，它相对热稳定，对链霉蛋白酶敏感，在Sephadex G-75和G-200柱色谱上的表观分子量为30至50 kDa。PF BAL诱导MBMMC释放β-己的能力不依赖于IgE，因为与用IgE致敏的MBMMC相比，未致敏或经乳酸处理的MBMMC释放的β-己量相似。因此，PF患者的BAL液含有一种HRF，它通过不依赖IgE的机制诱导MBMMC释放β-己。HRF的存在可以解释PF患者BAL组胺水平升高的原因。
