Lectin induced complement pathway
The complement system is the major effector of the humoral branch of the immune
system, acting to protect the host from microorganisms such as bacteria.
Complement components are designated by numerals
(C1-C9), by letter symbols
(e.g., Complement factor I (Factor I)), or by trivial names.
Peptide fragments formed by activation of a component are denoted by small letters , .
In most cases, the smaller fragment resulting from cleavage of a Complement component
is designated 'a' and the larger fragment designated 'b' (e.g.,
C3a, C3b; note that
C2 is an exception: C2a is the
larger cleavage fragment) .
Larger fragments bind to targets near activation sites, while smaller fragments,
called anaphylatoxins, diffuse from the site and may initiate localized inflammatory
responses by binding to specific receptors, such as Complement component 3a receptor 1
Complement component 5a receptor 1 (CR5aR)
, , . Complement fragments named
opsonins, i.e., C3b, C3dg, and
iC3b, interact with the cell surface receptors, such as
Complement component receptor 1
(CR1), Complement component receptor 2
(CD21), Integrins alpha-M/beta-2
integrin and alpha-X/beta-2 integrin, to
promote phagocytosis .
Complement fragments interact with one another to form functional complexes.
Lectins such as Ficolin 3 (H-Ficolin), Ficolin 2
(L-Ficolin) and Mannose-binding
lectin 2 soluble
proteins that recognize and bind to specific carbohydrate targets . The
lectin pathway, like the alternative pathway, does not depend on antibodies for its
activation. The lectin pathway is activated by the binding of
MBL2 to mannose residues on glycoproteins or carbohydrates
on the surface of microorganisms , .
MBL2 is an acute phase protein produced in inflammatory
responses. Its function in the complement pathway is similar to that of Complement
component 1 q subcomponent (C1q), which it resembles in
structure . After MBL2 binds to the surface
of a cell or pathogen, Mannan-binding lectin serine peptidase 1 and 2
(MASP1 and MASP2), bind to
MBL2 . The active complex formed by this
association causes cleavage and activation of C4 and
C2. The MASP1 and
MASP2 proteins have structural similarity to Complement
component 1 r subcomponent (C1r) and Complement component 1
s subcomponent (C1s) and mimic their activities.
C3 convertase (C2aC4b) and C5 convertase
(C2aC4bC3b) are formed via assembly of
C4b, C2a and
additional C3b molecules without specific
antibody binding. This mechanism represents an important innate defense mechanism
comparable to the alternative complement pathway , , , .
Smaller fragments resulting from complement cleavage, C3a
and C5a, called anaphylatoxins, bind to
receptors CR3aR and CR5aR on
the surface of mast cells and blood basophils. These complement components induce
degranulation, with release of histamine and other biologically active mediators .
Factor I is a major regulator of complement. As a
protease it has very restricted specificity, cleaving only C3b
or C4b in the
presence of a cofactor such as Complement factor H (Factor
H). Cleavage of C3b by Factor I
yields iC3b, a major
The classical, alternative, or lectin complement pathways lead to the production of an
active C5 convertase (C2aC4bC3b) . The
terminal sequence of complement activation involves Complement components
C7, C8, and C9,
which interact sequentially to form a macromolecular structure
called Membrane attack complex. This complex creates pores
in the cell membrane and induces cell lysis. C5b initiates
assembly of Membrane attack complex by binding of
C6 and C7 resulting in
C5b/C6/C7 hydrophobic complex. It inserts into the lipid bilayer of cell membranes, where
it becomes a high-affinity receptor for C8 molecules
C8gamma). C5b/C6/C7/C8 complex has a limited ability to lyse
cells. The formation of fully active Membrane attack complex
is accomplished by binding of C9 to C5b/C6/C7/C8 complex.
This fully active Membrane attack complex forms a large
channel through the membrane of the target cell, enabling ions and small molecules to
diffuse freely across the membrane .
The latest step of complement activation is also controlled by the membrane-associated
complement regulatory protein CD59 that prevents the
formation of the Membrane attack complex at the terminal
step of complement activation cascade , . Plasma
complement regulatory protein Clusterin can also interfere
with formation of the Membrane attack complex pore .
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