Specific inhibition of interleukin 3 bioactivity by a monoclonal antibody reactive with hematopoietic progenitor cells.
Specific inhibition of interleukin 3 bioactivity by a monoclonal antibody reactive with hematopoietic progenitor cells.
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通过与造血祖细胞反应的单克隆抗体特异性抑制白细胞介素 3 的生物活性。
DOI：
10.1073/pnas.87.12.4449
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发表时间：
1990
影响因子：
11.1
通讯作者：
Zuckerman,KS
中科院分区：
文献类型：
--
作者：
Emanuel,PD;Peiper,SC;Chen,Z;Sheng,DC;Zuckerman,KS
HIM1最初被命名为HI98，是一种针对人单核细胞的鼠源性IgM抗体，在第四届国际白细胞分型研讨会(称为抗体M0141)上报道，HIM1是157种抗体中唯一一种抑制IL-3与KG-1人急性髓系白血病细胞和正常人单核细胞结合的抗体。我们对HIM1在IL-3介导的造血祖细胞刺激中的选择性作用进行了详细的研究。去除贴壁细胞和T细胞的正常人骨髓单个核细胞与HIM1抗体共孵育后，对IL-3介导的红系祖细胞(最大抑制率为55%)和粒/巨噬细胞集落形成单位(最大抑制率为49%)的刺激均呈剂量依赖性抑制。HIM1抗体对红系集落形成单位的生长无影响。此外，用HIM1抗体预先孵育细胞对粒细胞/巨噬细胞集落刺激因子诱导的红细胞破裂或粒细胞/巨噬细胞集落生长均无不良影响。为了确保HIM1抗体不会直接与IL-3本身发生反应，我们尝试使用免疫耗竭来去除已添加到我们的培养基中的IL-3。虽然我们能够通过免疫去除结合到琼脂糖珠上的抗IL-3抗体来去除IL-3的生物活性，但是带有HIM1的珠子并不能从介质中去除IL-3的活性。中性粒细胞结合高水平的HIM1，尽管它们只有很少或根本没有可检测到的IL-3受体。因此，这种抗体似乎识别一种细胞表面抗原，该抗原对最佳的IL-3结合和生物活性至关重要，但不是真正的IL-3受体。
HIM1, originally designated HI98, a murine monoclonal IgM antibody raised against human mononuclear cells, has been reported at the Fourth International Leukocyte Typing Workshop (called antibody M0141) to be the only one of 157 antibodies tested that inhibited binding of interleukin 3 (IL-3) to KG-1 human acute myelogenous leukemia cells and normal human monocytes. We have carried out detailed studies of the selective effect of HIM1 on IL-3-mediated stimulation of hematopoietic progenitors. Preincubation of normal human bone marrow mononuclear cells, depleted of adherent cells and T cells, with HIM1 antibody resulted in a dose-dependent inhibition of IL-3-mediated stimulation of both erythroid burst-forming units (maximum inhibition 55%) and granulocyte/macrophage colony-forming units (maximum inhibition 49%). HIM1 antibody had no effect on growth of erythroid colony-forming units in culture. In addition, preincubation of the cells with HIM1 antibody had no deleterious effect on granulocyte/macrophage colony-stimulating factor-induced growth of either erythroid bursts or granulocyte/macrophage colonies. To be certain that the HIM1 antibody did not react directly with IL-3 itself, we attempted to use immunodepletion to remove IL-3 that had been added to our culture medium. Although we were able to remove IL-3 bioactivity by immunodepletion with anti-IL-3 antibody bound to Sepharose beads, beads with attached HIM1 did not remove IL-3 activity from the medium. Polymorphonuclear neutrophils bind high levels of HIM1, although they have very few or no detectable IL-3 receptors. Therefore, this antibody appears to recognize a cell surface antigen that is critical for optimal IL-3 binding and bioactivity but is not the actual IL-3 receptor.