We read with great interest the article by Hayashi et al. (1), in which the authors report the generation of two new mouse strains, specifically deficient in MASP-1 or MASP-3. In their study, the authors demonstrated in mice that MASP-1 is indispensable for lectin pathway activation, and MASP-3 is responsible for proteolytic processing of zymogen FD (pro-FD) to FD, the initiating protease of the alternative pathway.

The authors’ findings in these mouse models are in perfect agreement with our previous results obtained with human whole blood, plasma, and serum samples using specific human MASP-1, MASP-2, and MASP-3 inhibitors developed by directed evolution (2, 3). In our prior studies, we showed that a monospecific MASP-1 inhibitor completely prevented lectin pathway activation (2). Using a specific MASP-3 inhibitor, we also demonstrated that MASP-3 is the exclusive activator of pro-FD in resting human blood (3). A publication by another research group also highlighted the important role of MASP-3 in pro-FD activation (4).

The only apparent difference between the previous human results and the new mouse results is the role of MASP-1 in LPS-driven alternative pathway activation (5). In this respect, the mouse and the human complement systems might be different, but not necessarily at the level of MASP-1 (68).

In all, by comparing our and other previous human results with the new mouse results of Hayashi et al. (1), we conclude that the major functions of MASP-1 and MASP-3 have been conserved during mammalian evolution, although minor species-specific differences may exist.

Abbreviation used in this article:

pro-FD

zymogen FD.

1
Hayashi
,
M.
,
T.
Machida
,
Y.
Ishida
,
Y.
Ogata
,
T.
Omori
,
M.
Takasumi
,
Y.
Endo
,
T.
Suzuki
,
M.
Sekimata
,
Y.
Homma
, et al
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2019
.
Cutting edge: role of MASP-3 in the physiological activation of factor D of the alternative complement pathway
.
J. Immunol.
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1416
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2
Héja
,
D.
,
A.
Kocsis
,
J.
Dobó
,
K.
Szilágyi
,
R.
Szász
,
P.
Závodszky
,
G.
Pál
,
P.
Gál
.
2012
.
Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2
.
Proc. Natl. Acad. Sci. USA
109
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10498
10503
.
3
Dobó
,
J.
,
D.
Szakács
,
G.
Oroszlán
,
E.
Kortvely
,
B.
Kiss
,
E.
Boros
,
R.
Szász
,
P.
Závodszky
,
P.
Gál
,
G.
Pál
.
2016
.
MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked
.
Sci. Rep.
6
:
31877
.
4
Pihl
,
R.
,
L.
Jensen
,
A. G.
Hansen
,
I. B.
Thøgersen
,
S.
Andres
,
F.
Dagnæs-Hansen
,
K.
Oexle
,
J. J.
Enghild
,
S.
Thiel
.
2017
.
Analysis of factor D isoforms in Malpuech–Michels–Mingarelli–Carnevale patients highlights the role of MASP-3 as a maturase in the alternative pathway of complement
.
J. Immunol.
199
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2158
2170
.
5
Paréj
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K.
,
A.
Kocsis
,
C.
Enyingi
,
R.
Dani
,
G.
Oroszlán
,
L.
Beinrohr
,
J.
Dobó
,
P.
Závodszky
,
G.
Pál
,
P.
Gál
.
2018
.
Cutting edge: a new player in the alternative complement pathway, MASP-1 is essential for LPS-induced, but not for zymosan-induced, alternative pathway activation
.
J. Immunol.
200
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2247
2252
.
6
Kimura
,
Y.
,
T.
Miwa
,
L.
Zhou
,
W. C.
Song
.
2008
.
Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement
.
Blood
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7
Ferreira
,
V. P.
,
C.
Cortes
,
M. K.
Pangburn
.
2010
.
Native polymeric forms of properdin selectively bind to targets and promote activation of the alternative pathway of complement
.
Immunobiology
215
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940
.
8
Selander
,
B.
,
U.
Mårtensson
,
A.
Weintraub
,
E.
Holmström
,
M.
Matsushita
,
S.
Thiel
,
J. C.
Jensenius
,
L.
Truedsson
,
A. G.
Sjöholm
.
2006
.
Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2
.
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