Terai Itaru, Kobayashi Kunihiko, Matsushita Masanao, Miyakawa Hiroshi, Mafune Naoki, Kikuta Hideaki
Institute of Medical Science, Health Sciences University of Hokkaido, Sapporo, Japan.
Eur J Immunol. 2003 Oct;33(10):2755-63. doi: 10.1002/eji.200323955.
Mannose-binding lectin (MBL) activates complement through MBL-associated serine proteases (MASP). A deficiency in MBL due to mutations at exon 1 of the human MBL gene is reported to cause vulnerability to infection. We examined sera of known MBL genotype by gel filtration and assessed their elution patterns using an ELISA for MBL and identified two MBL forms, a high-molecular-mass form and a lower-molecular-mass form. By the identification of either or both forms in individual sera, three types of patterns emerged: type 1 consisted of a high-molecular form; type 2, of a low-molecular form; and type 3, of both forms. Types 1, 2 and 3 corresponded, respectively, to a wild type (A/A), a homozygous mutation at codon 54 (B/B) and their heterozygote (A/B). One exception was a heterozygous LXPA/LYPB phenotype that exhibited the type-2 pattern. Binding to mannan and MASP-1/3 occurred exclusively with the high-molecular form. An apparent MBL deficiency does not in fact representa deficiency in MBL molecules but rather the presence of circulating oligomeric mutant MBL with impaired function.
甘露糖结合凝集素（MBL）通过MBL相关丝氨酸蛋白酶（MASP）激活补体。据报道，由于人类MBL基因外显子1发生突变导致MBL缺乏会使人易受感染。我们通过凝胶过滤检查了已知MBL基因型的血清，并使用MBL ELISA评估其洗脱模式，鉴定出两种MBL形式，一种高分子质量形式和一种低分子质量形式。通过在个体血清中鉴定其中一种或两种形式，出现了三种类型的模式：1型由高分子形式组成；2型由低分子形式组成；3型由两种形式组成。1型、2型和3型分别对应野生型（A/A）、密码子54处的纯合突变（B/B）及其杂合子（A/B）。一个例外是杂合子LXPA/LYPB表型表现出2型模式。与甘露聚糖和MASP-1/3的结合仅发生在高分子形式中。明显的MBL缺乏实际上并不代表MBL分子缺乏，而是存在功能受损的循环寡聚突变MBL。
