Kusmartsev S, Ruiz de Morales J M, Rullas J, Danilets M G, Subiza J L
Department of Immunology, Hospital Clínico San Carlos, E-28040 Madrid, Spain.
Cancer Immunol Immunother. 1999 Dec;48(9):493-8. doi: 10.1007/s002620050597.
Sialoadhesin (sheep erythrocyte receptor, SER) is a macrophage-restricted adhesion molecule that binds certain sialylated ligands. It is borne by bone marrow stromal macrophages, promoting the interaction with developing myeloid cells, and by a subset of tissue macrophages involved in antigen presentation and activation of tumor-reactive T cells. The expression of sialoadhesin on SER+ macrophages is not constitutive but requires the continuous supply of a sialoadhesin-inducing serum factor. Tumor growth is often associated with marked alterations of myelopoiesis and impairment of T cell activation; yet the expression of sialoadhesin in macrophages derived from tumor bearers has not been addressed. The aim of this study was to assess whether Ehrlich tumor (ET) - a murine mammary carcinoma - growth may modify the sialoadhesin expression by bone marrow macrophages and/or sialoadhesin-inducing activity in ET-bearing sera. Moreover, putative functional sialoadhesin inhibitors produced by ET cells were tested. The results indicate that bone marrow cells from ET bearers show a seven- to eight-fold decrease in SER+ cells as detected by flow cytometry. This is accompanied by an overall decrease in sheep erythrocyte binding to tumor-bearer-derived bone marrow cells, but also by lower numbers of plastic-adherent cells. Functional sialoadhesin expression is preserved at the single-cell level and no inhibitors are found in ET-bearing sera or ET cell culture supernatants. Tumor progression does not impair the sialoadhesin-inducing activity of ET-bearing sera, or the ability of SER- macrophages (e.g. peritoneal macrophages) to respond to such an induction. In conclusion, while SER+ macrophages are greatly decreased in bone marrow from ET bearers, this is not due to a down-regulation of sialoadhesin expression, nor to an impairment of sialoadhesin-inducing factor or to the presence of sialoadhesin-binding moieties of tumor origin, but, more likely, to a decrease of fully mature macrophages.
唾液酸黏附素(绵羊红细胞受体,SER)是一种巨噬细胞限制性黏附分子,可结合某些唾液酸化配体。它由骨髓基质巨噬细胞产生,促进与发育中的髓样细胞相互作用,也由参与抗原呈递和肿瘤反应性T细胞激活的一部分组织巨噬细胞产生。SER+巨噬细胞上唾液酸黏附素的表达不是组成性的,而是需要持续供应一种诱导唾液酸黏附素的血清因子。肿瘤生长通常与骨髓生成的显著改变和T细胞激活受损有关;然而,肿瘤携带者来源的巨噬细胞中唾液酸黏附素的表达尚未得到研究。本研究的目的是评估艾氏肿瘤(ET)——一种小鼠乳腺癌——的生长是否会改变骨髓巨噬细胞中唾液酸黏附素的表达和/或荷瘤血清中诱导唾液酸黏附素的活性。此外,还测试了ET细胞产生的推定功能性唾液酸黏附素抑制剂。结果表明,通过流式细胞术检测,ET携带者的骨髓细胞中SER+细胞减少了7至8倍。这伴随着绵羊红细胞与肿瘤携带者来源的骨髓细胞结合的总体减少,但也伴随着贴壁细胞数量的减少。在单细胞水平上,功能性唾液酸黏附素的表达得以保留,并且在荷瘤血清或ET细胞培养上清液中未发现抑制剂。肿瘤进展不会损害荷瘤血清诱导唾液酸黏附素的活性,也不会损害SER-巨噬细胞(如腹膜巨噬细胞)对这种诱导的反应能力。总之,虽然ET携带者骨髓中SER+巨噬细胞大大减少,但这不是由于唾液酸黏附素表达下调,也不是由于诱导唾液酸黏附素因子受损或肿瘤来源的唾液酸黏附素结合部分的存在,而更可能是由于完全成熟巨噬细胞的减少。