Vancheri C, Ohtoshi T, Cox G, Xaubet A, Abrams J S, Gauldie J, Dolovich J, Denburg J, Jordana M
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Am J Respir Cell Mol Biol. 1991 Jan;4(1):11-7. doi: 10.1165/ajrcmb/4.1.11.
We have established primary lines of fibroblasts from nasal polyp (NP) tissues as well as from normal nasal (NN) mucosa and have examined the ability of these cells to release hormone-like peptide messenger molecules (cytokines). Our results show that human upper airway fibroblasts release granulocyte/macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and macrophage-CSF (M-CSF) in vitro. We also show that fibroblasts derived from NP tissue express the gene for GM-CSF at a higher level, and release the GM-CSF product in greater amounts, than NN fibroblasts. In addition, we have examined the ability of these fibroblasts and their conditioned medium (CM) to induce differentiation of human hemopoietic progenitor cells. After 7 d, cultures of these cells in RPMI-10% fetal bovine serum contained 5 +/- 2.5% (mean +/- SD) neutrophils. In contrast, culture of progenitor cells with fibroblasts resulted in significantly greater neutrophilic differentiation (18 +/- 4%). Culture in fibroblast-CM induced a similar degree of differentiation, and fibroblast-CM from NP fibroblasts elicited greater differentiation compared to CM from NN fibroblasts (17.5 +/- 3 versus 12 +/- 3%). The neutrophilic differentiation induced by fibroblast-CM can be fully inhibited by preincubating this CM with a monoclonal neutralizing antibody to human GM-CSF. Thus, our results demonstrate: (1) the ability of human upper airway fibroblasts to release GM-, G-, and M-CSF in vitro; (2) that fibroblasts derived from NP tissues express the gene and release the product GM-CSF at greater levels compared to NN fibroblasts; and (3) that fibroblast-derived GM-CSF causes neutrophilic differentiation of human hemopoietic progenitors.
我们已经从鼻息肉（NP）组织以及正常鼻黏膜（NN）中建立了成纤维细胞原代细胞系，并检测了这些细胞释放激素样肽信使分子（细胞因子）的能力。我们的结果表明，人上呼吸道成纤维细胞在体外可释放粒细胞/巨噬细胞集落刺激因子（GM-CSF）、粒细胞集落刺激因子（G-CSF）和巨噬细胞集落刺激因子（M-CSF）。我们还表明，与NN成纤维细胞相比，源自NP组织的成纤维细胞GM-CSF基因表达水平更高，且释放的GM-CSF产物量更大。此外，我们检测了这些成纤维细胞及其条件培养基（CM）诱导人造血祖细胞分化的能力。7天后，这些细胞在含10%胎牛血清的RPMI培养基中培养，中性粒细胞含量为5±2.5%（平均值±标准差）。相比之下，祖细胞与成纤维细胞共培养导致显著更高的嗜中性分化（18±4%）。在成纤维细胞-CM中培养诱导了相似程度的分化，与NN成纤维细胞的CM相比，NP成纤维细胞的成纤维细胞-CM诱导了更大程度的分化（17.5±3对12±3%）。成纤维细胞-CM诱导的嗜中性分化可通过将该CM与人GM-CSF单克隆中和抗体预孵育而完全抑制。因此，我们的结果表明：（1）人上呼吸道成纤维细胞在体外释放GM-CSF、G-CSF和M-CSF的能力；（2）与NN成纤维细胞相比，源自NP组织的成纤维细胞表达GM-CSF基因并释放更多水平的GM-CSF产物；（3）成纤维细胞衍生的GM-CSF导致人造血祖细胞嗜中性分化。
