MacGlashan D W
Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224.
J Allergy Clin Immunol. 1993 Feb;91(2):605-15. doi: 10.1016/0091-6749(93)90266-i.
Within the atopic and nonatopic population, basophils display a wide variation in the extent of histamine release when challenged with an optimal concentration of polyclonal anti-IgE antibody. We have tested the hypothesis that the maximum percent histamine release obtainable with this stimulus is an indicator of basophil sensitivity. We have defined basophil sensitivity, in the context of IgE-mediated release, as the number of cell-surface IgE molecules required to obtain a half-maximal IgE-mediated response, and we have examined this parameter in the basophils of 39 donors. Sensitizing basophils with various densities of antigen-specific IgE, and measuring histamine release at these measured densities, allowed a determination of basophil sensitivity in 38 of the donors. Basophil sensitivities ranged from 300 to 40,000 molecules per basophil (point of 50% maximal response), although most donors fell in the 800 to 8000 range, with 1900 molecules per basophil as the median response. The maximal response, after challenge with an optimal concentration of either polyclonal or monoclonal anti-IgE antibody, ranged from 8% to 94% (median, 50%). There was no correlation between basophil sensitivity and the maximum histamine release obtained by a challenge with anti-IgE antibody. Therefore two independent variables appeared to control the IgE-mediated response in basophils, similar to the parameters of efficacy and potency in drug studies. In the IgE-mediated response one parameter is the maximum histamine release obtainable through IgE-mediated mechanisms, and the second parameter is basophil sensitivity as defined above. As a byproduct of these studies, we also found that the density of unoccupied high-affinity receptors for IgE antibody was uncorrelated with the total receptor density (range, 4200 to 572,000 receptors per basophil). Indeed, the density of unoccupied receptors was remarkably constant across this large range of total receptor densities.
在特应性和非特应性人群中，当用最佳浓度的多克隆抗IgE抗体进行刺激时，嗜碱性粒细胞释放组胺的程度存在很大差异。我们检验了这样一个假设，即这种刺激所能获得的最大组胺释放百分比是嗜碱性粒细胞敏感性的一个指标。在IgE介导的释放背景下，我们将嗜碱性粒细胞敏感性定义为获得半数最大IgE介导反应所需的细胞表面IgE分子数量，并且我们在39名供体的嗜碱性粒细胞中检测了这一参数。用不同密度的抗原特异性IgE致敏嗜碱性粒细胞，并在这些测量密度下测量组胺释放，从而确定了38名供体的嗜碱性粒细胞敏感性。嗜碱性粒细胞敏感性范围为每个嗜碱性粒细胞300至40,000个分子（最大反应的50%点），尽管大多数供体处于800至8000的范围内，每个嗜碱性粒细胞1900个分子为中位反应。在用最佳浓度的多克隆或单克隆抗IgE抗体刺激后，最大反应范围为8%至94%（中位数为50%）。嗜碱性粒细胞敏感性与用抗IgE抗体刺激所获得的最大组胺释放之间没有相关性。因此，两个独立变量似乎控制着嗜碱性粒细胞中IgE介导的反应，这类似于药物研究中的疗效和效价参数。在IgE介导的反应中，一个参数是通过IgE介导机制所能获得的最大组胺释放，第二个参数是如上所定义的嗜碱性粒细胞敏感性。作为这些研究的一个副产品，我们还发现未占据的IgE抗体高亲和力受体密度与总受体密度无关（范围为每个嗜碱性粒细胞4200至572,000个受体）。事实上，在如此大范围的总受体密度中，未占据受体的密度非常恒定。
