Tanaka M, Suda T, Haze K, Nakamura N, Sato K, Kimura F, Motoyoshi K, Mizuki M, Tagawa S, Ohga S, Hatake K, Drummond A H, Nagata S
Osaka Bioscience Institute, Japan.
Nat Med. 1996 Mar;2(3):317-22. doi: 10.1038/nm0396-317.
The Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis in Fas-bearing cells. The membrane-bound human FasL was found to be converted to a soluble form (sFasL) by the action of a matrix metalloproteinase-like enzyme. Two neutralizing monoclonal anti-human FasL antibodies were identified, and an enzyme-linked immunosorbent assay (ELISA) for sFasL in human sera was established. Sera from healthy persons did not contain a detectable level of sFasL, whereas those from patients with large granular lymphocytic (LGL) leukemia and natural killer (NK) cell lymphoma did. These malignant cells constitutively expressed FasL, whereas peripheral NK cells from healthy persons expressed FasL only on activation. These results suggested that the systemic tissue damage seen in most patients with LGL leukemia and NK-type lymphoma is due to sFasL produced by these malignant cells. Neutralizing anti-FasL antibodies or matrix metalloproteinase inhibitors may be of use in modulating such tissue damage.
Fas配体（FasL）是肿瘤坏死因子家族的成员之一，可诱导表达Fas的细胞发生凋亡。人们发现，膜结合型人FasL在一种基质金属蛋白酶样酶的作用下可转化为可溶性形式（sFasL）。鉴定出两种中和性抗人FasL单克隆抗体，并建立了一种检测人血清中sFasL的酶联免疫吸附测定（ELISA）法。健康人的血清中未检测到可检测水平的sFasL，而大颗粒淋巴细胞（LGL）白血病和自然杀伤（NK）细胞淋巴瘤患者的血清中则含有sFasL。这些恶性细胞组成性表达FasL，而健康人的外周NK细胞仅在激活时表达FasL。这些结果表明，大多数LGL白血病和NK型淋巴瘤患者出现的全身性组织损伤是由这些恶性细胞产生的sFasL所致。中和性抗FasL抗体或基质金属蛋白酶抑制剂可能有助于调节此类组织损伤。
