Lukacs N W, Kunkel S L, Strieter R M, Evanoff H L, Kunkel R G, Key M L, Taub D D
Department of Pathology, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor, MI USA.
Blood. 1996 Mar 15;87(6):2262-8.
Mast cells play a critical role in allergic airway responses via IgE-specific activation and release of potent inflammatory mediators. In the present study, we have isolated and characterized primary mast cell lines derived from the upper airways of normal mice. The primary mast cell lines were grown and maintained by incubation with interleukin-3 (IL-3) and stem cell factor (SCF) and shown to be c-kit (SCF receptor) positive by flow cytometry. Subsequently, we examined the proliferation of both airway and bone marrow derived mast cell lines in response to inflammatory and hematopoietic cytokines, including SCF, IL-1, IL-3, interferon-gamma, IL-4, and IL-10. The results from the pulmonary mast cell lines were compared with those from bone marrow derived mast cells. Pulmonary mast cell lines were capable of proliferating in response to IL-3, IL-4, IL-10, and SCF, whereas the combination of SCF with the other cytokines did not increase the response over SCF alone. In contrast, the bone marrow-derived mast cells proliferated strongest to SCF or IL-3, but only modestly to IL-4 and IL-10. Furthermore, the combination of SCF with IL-3, but not the other cytokines, exhibited an increase in bone marrow-derived mast cell proliferation. Cytokine-specific stimulation of histamine release in the airway-derived and bone marrow-derived mast cells showed parallel results. SCF was the only cytokine shown to induce substantial histamine release. However, when certain nonhistamine releasing cytokines were combined with SCF, a synergistic increase in histamine release was induced in upper airway, but not bone marrow-derived mast cells. The results of these studies suggest that cytokines differentially modulate induction of proliferation and degranulation of bone marrow and upper airway-derived mast cells and may further indicate a cytokine activational cascade in tissue mast cells.
肥大细胞通过IgE特异性激活和释放强效炎症介质，在过敏性气道反应中发挥关键作用。在本研究中，我们分离并鉴定了源自正常小鼠上呼吸道的原代肥大细胞系。原代肥大细胞系通过与白细胞介素-3（IL-3）和干细胞因子（SCF）共同孵育来生长和维持，并通过流式细胞术显示为c-kit（SCF受体）阳性。随后，我们检测了气道和骨髓来源的肥大细胞系对包括SCF、IL-1、IL-3、干扰素-γ、IL-4和IL-10在内的炎症和造血细胞因子的增殖反应。将肺肥大细胞系的结果与骨髓来源的肥大细胞的结果进行了比较。肺肥大细胞系能够对IL-3、IL-4、IL-10和SCF作出增殖反应，而SCF与其他细胞因子的组合并未比单独使用SCF增加反应。相比之下，骨髓来源的肥大细胞对SCF或IL-3增殖最强，但对IL-4和IL-10的增殖反应较弱。此外，SCF与IL-3的组合而非其他细胞因子，可使骨髓来源的肥大细胞增殖增加。对气道来源和骨髓来源的肥大细胞中组胺释放的细胞因子特异性刺激显示出类似结果。SCF是唯一能诱导大量组胺释放的细胞因子。然而，当某些不释放组胺的细胞因子与SCF联合使用时，在上呼吸道来源的肥大细胞中可诱导组胺释放协同增加，但在骨髓来源的肥大细胞中则不然。这些研究结果表明，细胞因子对骨髓和上呼吸道来源的肥大细胞的增殖和脱颗粒诱导具有不同的调节作用，并且可能进一步表明组织肥大细胞中存在细胞因子激活级联反应。
