A journey through the lectin pathway of complement—MBL and beyond

Abstract

Mannose-binding lectin (MBL), collectin-10, collectin-11, and the ficolins (ficolin-1, ficolin-2, and ficolin-3) are soluble pattern recognition molecules in the lectin complement pathway. These proteins act as mediators of host defense and participate in maintenance of tissue homeostasis. They bind to conserved pathogen-specific structures and altered self-antigens and form complexes with the pentraxins to modulate innate immune functions. All molecules exhibit distinct expression in different tissue compartments, but all are found to a varying degree in the circulation. A common feature of these molecules is their ability to interact with a set of serine proteases named MASPs (MASP-1, MASP-2, and MASP-3). MASP-1 and -2 trigger the activation of the lectin pathway and MASP-3 may be involved in the activation of the alternative pathway of complement. Furthermore, MASPs mediate processes related to coagulation, bradykinin release, and endothelial and platelet activation. Variant alleles affecting expression and structure of the proteins have been associated with a variety of infectious and non-infectious diseases, most commonly as disease modifiers. Notably, the severe 3MC (Malpuech, Michels, Mingarelli, and Carnevale) embryonic development syndrome originates from rare mutations affecting either collectin-11 or MASP-3, indicating a broader functionality of the complement system than previously anticipated. This review summarizes the characteristics of the molecules in the lectin pathway.

Production of complement components by cells of the immune system

“…The recognition molecule for the CP is C1q, which upon binding to ligands such as surface-bound immunoglobulin (Ig)M, hexameric IgG or pentraxins, such as C-reactive protein and pentraxin-3, trigger CP activation [2]. Several recognition molecules have been described for the LP, including mannose-binding lectin (MBL), ficolins-1, 2 and 3 and collectins (CL-10, CL-11) [3]. The AP is activated spontaneously via a tick-over activation mechanism, but a role for properdin (FP) has also been proposed [4].…”

Chimeric Proteins Containing MAP-1 and Functional Domains of C4b-Binding Protein Reveal Strong Complement Inhibitory Capacities

“…The LP is initiated by two groups of pattern recognition molecules (PRM): c-type lectins, such as mannose-binding lectin (MBL), collectin-10 (CL-10, CL-L1), and collectin-11 (CL-11, CL-K1) and ficolins, i.e., ficolin-1 (M-ficolin), ficolin-2 (L-ficolin), and ficolin-3 (H-ficolin or Hakata antigen). Binding of PRMs to ligands activates the MBL-associated serine proteases (MASPs), causing cleavage and activation of C2 and C4 (10). The AP is constantly “probing” surfaces in a non-specific fashion by means of a constitutive low level of spontaneous hydrolysis of C3 into the C3b analog C3(H 2 O) (11).…”

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

“…This can explain the small, however non‐significant, early increase of FCN1 in patients. FCN2 is synthesized in the liver as a soluble protein 40. Increased secretion of FCN2 is, in relation to FCN1, delayed, which enables a consumption profile early after MI.…”