Walker A M, Montgomery D W, Saraiya S, Ho T W, Garewal H S, Wilson J, Lorand L
Division of Biomedical Sciences, University of California, Riverside 92521-0121, USA.
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3278-82. doi: 10.1073/pnas.92.8.3278.
Several lines of evidence indicate that immunoglobulin-bound prolactin found in human serum is not a conventional complex between an anti-prolactin antibody and prolactin but a different type of association of prolactin with the Fab portion of IgG heavy chains. The complex of prolactin with IgG was purified from serum by anti-human prolactin affinity chromatography and was shown to contain close to 1 mole of N epsilon-(gamma-glutamyl)lysine crosslinks per mole of complex, a characteristic feature in structures crosslinked by transglutaminase. Interestingly, the complex caused a proliferation of cells from a subset of patients with chronic lymphocytic leukemia, while it was inactive in a cell proliferation prolactin bioassay. By contrast, human prolactin stimulated the proliferation of cells in the bioassay but had no effect on the complex-responsive cells from the patients. Competition studies with prolactin and free Fc fragment of IgG demonstrated a necessity for engaging both the prolactin and the immunoglobulin receptors for proliferation. More importantly, competition for the growth response by free prolactin and IgG suggests both possible reasons for the slow growth of this neoplasm as well as avenues for control of the disease.
多条证据表明，人血清中发现的免疫球蛋白结合型催乳素并非抗催乳素抗体与催乳素之间的传统复合物，而是催乳素与IgG重链Fab部分的一种不同类型的结合。通过抗人催乳素亲和层析从血清中纯化出催乳素与IgG的复合物，结果显示每摩尔复合物含有近1摩尔的Nε-（γ-谷氨酰基）赖氨酸交联键，这是转谷氨酰胺酶交联结构的一个特征。有趣的是，该复合物可导致一部分慢性淋巴细胞白血病患者的细胞增殖，而在细胞增殖催乳素生物测定中却无活性。相比之下，人催乳素在生物测定中可刺激细胞增殖，但对这些患者的复合物反应性细胞没有影响。催乳素与IgG游离Fc片段的竞争研究表明，细胞增殖需要同时激活催乳素受体和免疫球蛋白受体。更重要的是，游离催乳素和IgG对生长反应的竞争既提示了这种肿瘤生长缓慢的可能原因，也为疾病控制提供了途径。
