Cutting Edge: Role of MASP-3 in the Physiological Activation of Factor D of the Alternative Complement Pathway

被引：39

作者：

Hayashi, Manabu ^{[1
,2
]}

Machida, Takeshi ^{[1
]}

Ishida, Yumi ^{[1
]}

Ogata, Yusuke ^{[1
]}

Omori, Tomoko ^{[1
]}

Takasumi, Mika ^{[1
,2
]}

Endo, Yuichi ^{[1
]}

Suzuki, Toshiyuki ^{[3
]}

Sekimata, Masayuki ^{[3
]}

Homma, Yoshimi ^{[4
]}

Ikawa, Masahito ^{[5
]}

Ohira, Hiromasa ^{[2
]}

Fujita, Teizo ^{[6
]}

Sekine, Hideharu ^{[1
]}

机构：

[1] Fukushima Med Univ, Sch Med, Dept Immunol, 1 Hikarigaoka, Fukushima, Fukushima 9601295, Japan

[2] Fukushima Med Univ, Sch Med, Dept Gastroenterol, Fukushima, Fukushima 9601295, Japan

[3] Fukushima Med Univ, Sch Med, Radioisotope Res Ctr, Fukushima, Fukushima 9601295, Japan

[4] Fukushima Med Univ, Sch Med, Dept Biomol Sci, Fukushima, Fukushima 9601295, Japan

[5] Osaka Univ, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan

[6] Fukushima Prefectural Gen Hyg Inst, Fukushima, Fukushima 9608141, Japan

来源：

JOURNAL OF IMMUNOLOGY | 2019年 / 203卷 / 06期

基金：

日本学术振兴会;

关键词：

LECTIN PATHWAY; DEFICIENT; SYSTEM;

D O I：

10.4049/jimmunol.1900605

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The complement system, a part of the innate immune system, can be activated via three different pathways. In the alternative pathway, a factor D (FD) plays essential roles in both the initiation and the amplification loop and circulates as an active form. Mannose-binding lectin-associated serine proteases (MASPs) are key enzymes of the lectin pathway, and MASP-1 and/or MASP-3 are reported to be involved in the activation of FD. In the current study, we generated mice mono-specifically deficient for MASP-1 or MASP-3 and found that the sera of the MASP-1-deficient mice lacked lectin pathway activity, but those of the MASP-3-deficient mice lacked alternative pathway activity with a zymogen FD. Furthermore, the results indicate that MASP-3 but not MASP-1 activates the zymogen FD under physiological conditions and MASP-3 circulates predominantly as an active form. Therefore, our study illustrates that, in mice, MASP-3 orchestrates the overall complement reaction through the activation of FD.

引用

页码：1411 / 1416

页数：6