Bagby G C, Bennett R M
Blood. 1982 Jul;60(1):108-12.
Neutrophil extracts were prepared from the peripheral blood of 40 normal volunteers and tested for their ability to inhibit CSA production by mononuclear leukocytes. Highly dilute neutrophil extracts inhibited CSA production/release, while extracts selectively depleted of lactoferrin by antibody affinity chromatography did not. In addition, higher concentrations of neutrophil extracts and higher doses of lactoferrin (10(-9)-10(-6) M) failed to inhibit CSA production/release. We found no evidence of CSA or CSA-enhancing factors in either our lactoferrin or our neutrophil extracts. However, using gel chromatography and rate zonal density sedimentation, we noted that lactoferrin undergoes concentration-dependent polymerization at 10(-9)-10(-10) M in tissue culture medium and that while monomeric lactoferrin effectively inhibits CSA production/release in vitro, the polymeric form does not. Thus, while we have confirmed that lactoferrin is the activity in neutrophil extracts that inhibits CSA production, we have also found that lactoferrin undergoes reversible polymerization at physiologic concentrations and that the polymerized molecule is inactive. The tendency of lactoferrin to polymerize in tissue culture medium and in vivo should be taken into account in any studies on its potential role as a physiologically relevant regulator of granulopoiesis.
从40名正常志愿者的外周血中制备中性粒细胞提取物，并检测其抑制单核白细胞产生CSA的能力。高度稀释的中性粒细胞提取物可抑制CSA的产生/释放，而通过抗体亲和层析选择性去除乳铁蛋白的提取物则不能。此外，更高浓度的中性粒细胞提取物和更高剂量的乳铁蛋白（10^(-9)-10^(-6) M）未能抑制CSA的产生/释放。我们在乳铁蛋白提取物或中性粒细胞提取物中均未发现CSA或CSA增强因子的证据。然而，通过凝胶色谱法和速率区带密度沉降法，我们注意到乳铁蛋白在组织培养基中于10^(-9)-10^(-10) M时会发生浓度依赖性聚合，并且虽然单体乳铁蛋白在体外可有效抑制CSA的产生/释放，但聚合形式则不能。因此，虽然我们已证实乳铁蛋白是中性粒细胞提取物中抑制CSA产生的活性成分，但我们也发现乳铁蛋白在生理浓度下会发生可逆聚合，且聚合分子无活性。在任何关于乳铁蛋白作为粒细胞生成生理相关调节因子潜在作用的研究中，都应考虑其在组织培养基和体内聚合的趋势。
