Sillaber C, Geissler K, Scherrer R, Kaltenbrunner R, Bettelheim P, Lechner K, Valent P
Medical Department, University of Vienna, Austria.
Blood. 1992 Aug 1;80(3):634-41.
Basophils and eosinophils share a common differentiation pathway. Factors regulating terminal commitment toward one cell type, however, have so far not been defined. Interleukin-3 (IL-3) is a potent differentiation factor for both human eosinophils and basophils. In the present study, the effects of various recombinant human (rh) growth regulators on IL-3-dependent growth of eosinophils and basophils were studied in a bone marrow (BM) suspension culture system (normal donors, n = 13). We found that type beta transforming growth factors (TGFs) lead to a significant increase in the absolute numbers of basophils in BM cultures grown in the presence of IL-3 (day 14 of culture; IL-3: 133 +/- 20 v IL-3 + TGF-beta 1: 231 +/- 28 x 10(3)/mL [P less than .01]) and to an increase in the total histamine values (IL-3: 72.6 +/- 22.2 v IL-3 + TGF-beta 1: 142.9 +/- 37.3 ng/mL [P less than .015]) compared with rhIL-3 alone. In contrast, type beta TGFs were found to inhibit the IL-3-dependent growth of eosinophils (IL-3: 170.4 +/- 37.2 v IL-3 + TGF-beta 1: 16.7 +/- 5.2 x 10(3)/mL [P less than .01]) and formation of eosinophil cationic protein in the same culture system. The effect of TGF-beta 1 (and TGF-beta 2) on IL-3-dependent differentiation of basophils and eosinophils was dose- and time-dependent (maximum effects observed with 1 to 10 ng/mL of rhTGF-beta 1 or TGF-beta 2) and could be neutralized by an antibody specific for TGF-beta 1. In contrast to the TGFs, interferon-alpha (IFN-alpha) and IFN-gamma were found to downregulate IL-3-dependent formation of both basophils (IL-3: 167 +/- 33 v IL-3 + IFN-alpha: 67 +/- 25 v IL-3 + IFN-gamma: 65 +/- 33 x 10(3)/mL [P less than .01]) and eosinophils (IL-3: 239 +/- 5 v IL-3 + IFN-alpha: 81 +/- 4 v IL-3 + IFN-gamma: 67 +/- 17 x 10(3)/mL [P less than .05]) in our culture system. Type beta TGFs as well as the IFNs failed to directly induce differentiation of human basophils or eosinophils in the absence of other growth factors. Together, these results show that type beta TGFs and IFNs are potent regulators of cytokine-dependent growth and differentiation of human allergic effector cells.
嗜碱性粒细胞和嗜酸性粒细胞具有共同的分化途径。然而，迄今为止，尚未明确调节向一种细胞类型终末分化的因子。白细胞介素-3（IL-3）是人类嗜酸性粒细胞和嗜碱性粒细胞的有效分化因子。在本研究中，在骨髓（BM）悬浮培养系统（正常供体，n = 13）中研究了各种重组人（rh）生长调节剂对IL-3依赖的嗜酸性粒细胞和嗜碱性粒细胞生长的影响。我们发现，β型转化生长因子（TGFs）导致在IL-3存在下培养的BM培养物中嗜碱性粒细胞的绝对数量显著增加（培养第14天；IL-3：133±20对IL-3 + TGF-β1：231±28×10³/mL [P <.01]），并且与单独的rhIL-3相比，总组胺值增加（IL-3：72.6±22.2对IL-3 + TGF-β1：142.9±37.3 ng/mL [P <.015]）。相反，发现β型TGFs抑制嗜酸性粒细胞的IL-3依赖生长（IL-3：170.4±37.2对IL-3 + TGF-β1：16.7±5.2×10³/mL [P <.01]）以及同一培养系统中嗜酸性粒细胞阳离子蛋白的形成。TGF-β1（和TGF-β2）对IL-3依赖的嗜碱性粒细胞和嗜酸性粒细胞分化的影响是剂量和时间依赖性的（在1至10 ng/mL的rhTGF-β1或TGF-β2时观察到最大效应），并且可以被TGF-β1特异性抗体中和。与TGFs相反，发现干扰素-α（IFN-α）和干扰素-γ下调IL-3依赖的嗜碱性粒细胞（IL-3：167±33对IL-3 + IFN-α：67±25对IL-3 + IFN-γ：65±33×10³/mL [P <.01]）和嗜酸性粒细胞（IL-3：239±5对IL-3 + IFN-α：81±4对IL-3 + IFN-γ：67±17×10³/mL [P <.05]）的形成。在没有其他生长因子的情况下，β型TGFs以及IFNs未能直接诱导人类嗜碱性粒细胞或嗜酸性粒细胞的分化。总之，这些结果表明，β型TGFs和IFNs是细胞因子依赖的人类过敏效应细胞生长和分化的有效调节因子。
