Piacvezérelt kutatás-fejlesztési és innovációs projektek támogatása(2020-1.1.2-PIACI-KFI-2021-00273)
Támogató: Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal
National Laboratory of Translational Neuroscience(RRF-2.3.1-21-2022-00015)
(K115623)
(TKP2021-EGA-24)
The complement system is the other major proteolytic cascade in the blood of vertebrates
besides the coagulation–fibrinolytic system. Among the three main activation routes
of complement, the lectin pathway (LP) has been discovered the latest, and it is still
the subject of intense research. Mannose-binding lectin (MBL), other collectins, and
ficolins are collectively termed as the pattern recognition molecules (PRMs) of the
LP, and they are responsible for targeting LP activation to molecular patterns, e.g.,
on bacteria. MBL-associated serine proteases (MASPs) are the effectors, while MBL-associated
proteins (MAps) have regulatory functions. Two serine protease components, MASP-1
and MASP-2, trigger the LP activation, while the third component, MASP-3, is involved
in the function of the alternative pathway (AP) of complement. Besides their functions
within the complement system, certain LP components have secondary (“moonlighting”)
functions, e.g., in embryonic development. They also contribute to blood coagulation,
and some might have tumor suppressing roles. Uncontrolled complement activation can
contribute to the progression of many diseases (e.g., stroke, kidney diseases, thrombotic
complications, and COVID-19). In most cases, the lectin pathway has also been implicated.
In this review, we summarize the history of the lectin pathway, introduce their components,
describe its activation and regulation, its roles within the complement cascade, its
connections to blood coagulation, and its direct cellular effects. Special emphasis
is placed on disease connections and the non-canonical functions of LP components.