Hogaboam C, Kunkel S L, Strieter R M, Taub D D, Lincoln P, Standiford T J, Lukacs N W
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
J Immunol. 1998 Jun 15;160(12):6166-71.
Mast cell activation can be induced by multiple mechanisms, including IgE-, complement-, and stem cell factor (SCF)-mediated pathways. In addition, the interaction of mast cells with particular cell populations, such as fibroblasts, have also demonstrated increased mast cell reactivity. In these studies, we have investigated the role of fibroblast-mast cell interaction for induction of histamine release and chemokine production and the specific role of SCF during this interaction. Primary pulmonary fibroblast cell lines were grown in culture and used throughout these studies. Mast cells were grown in parallel with fibroblasts by incubation of bone marrow cells with SCF and IL-3. During mast cell-fibroblast coculture, increased histamine release could be attenuated either by separation of the cell populations using a Trans-Well setup, which did not allow cellular contact, or by specific anti-SCF Ab. In addition, a significant increase in eotaxin, a potent eosinophil-specific C-C chemokine, was also observed during fibroblast-mast cell interaction. The production of eotaxin was cell contact dependent and could be inhibited using an anti-SCF Ab or specific antisense therapy. SCF was constitutively produced from fibroblasts in its transmembrane form and could be induced by TNF. SCF-coated plates induced significant mast cell-derived eotaxin production, whereas soluble SCF induced little or no eotaxin, suggesting a necessity for receptor cross-linking for activation. These studies indicate that fibroblast-mast cell contact plays a role in exacerbation of histamine release and eotaxin production.
肥大细胞活化可由多种机制诱导，包括免疫球蛋白E、补体和干细胞因子（SCF）介导的途径。此外，肥大细胞与特定细胞群体（如成纤维细胞）的相互作用也显示出肥大细胞反应性增加。在这些研究中，我们研究了成纤维细胞与肥大细胞相互作用在诱导组胺释放和趋化因子产生中的作用，以及SCF在此相互作用中的具体作用。原代肺成纤维细胞系在培养物中生长，并在整个研究中使用。通过将骨髓细胞与SCF和白细胞介素-3一起孵育，使肥大细胞与成纤维细胞平行生长。在肥大细胞与成纤维细胞共培养期间，组胺释放的增加可通过使用Trans-Well装置分离细胞群体（不允许细胞接触）或通过特异性抗SCF抗体来减弱。此外，在成纤维细胞与肥大细胞相互作用期间，还观察到嗜酸性粒细胞趋化因子（一种有效的嗜酸性粒细胞特异性C-C趋化因子）显著增加。嗜酸性粒细胞趋化因子的产生依赖于细胞接触，并且可以使用抗SCF抗体或特异性反义疗法来抑制。SCF以其跨膜形式由成纤维细胞组成性产生，并可由肿瘤坏死因子诱导。包被有SCF的平板可诱导肥大细胞产生大量的嗜酸性粒细胞趋化因子，而可溶性SCF几乎不诱导或不诱导嗜酸性粒细胞趋化因子，这表明受体交联激活是必要的。这些研究表明，成纤维细胞与肥大细胞的接触在组胺释放和嗜酸性粒细胞趋化因子产生的加剧中起作用。
