Essential Role of Mannose-binding Lectin-associated Serine Protease-1 in Activation of the Complement Factor D

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2009 Dec 30

PMID 20038603

Citations 76

Authors

Minoru Takahashi

Yumi Ishida

Daisuke Iwaki

Kazuko Kanno

Toshiyuki Suzuki

Yuichi Endo

Yoshimi Homma

Teizo Fujita

Affiliations

Soon will be listed here.

Abstract

The complement system is an essential component of innate immunity, participating in the pathogenesis of inflammatory diseases and in host defense. In the lectin complement pathway, mannose-binding lectin (MBL) and ficolins act as recognition molecules, and MBL-associated serine protease (MASP) is a key enzyme; MASP-2 is responsible for the lectin pathway activation. The function of other serine proteases (MASP-1 and MASP-3) is still obscure. In this study, we generated a MASP-1- and MASP-3-deficient mouse model (Masp1/3-/-) and found that no activation of the alternative pathway was observed in Masp1/3-/- serum. Mass spectrometric analysis revealed that circulating complement factor D (Df) in Masp1/3-/- mice is a zymogen (pro-Df) with the activation peptide QPRGR at its N terminus. These results suggested that Masp1/3-/- mice failed to convert pro-Df to its active form, whereas it was generally accepted that the activation peptide of pro-Df is removed during its secretion and factor D constitutively exists in an active form in the circulation. Furthermore, recombinant MASP-1 converted pro-Df to the active form in vitro, although the activation mechanism of pro-Df by MASP-1 is still unclear. Thus, it is clear that MASP-1 is an essential protease of both the lectin and alternative complement pathways.

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