Collectin

Collectins (collagen-containing C-type lectins) are a part of the innate immune system. They form a family of collagenous Ca²⁺-dependent defense lectins, which are found in animals. Collectins are soluble pattern recognition receptors (PRRs). Their function is to bind to oligosaccharide structure or lipids which are on the surface of microorganisms. Like other PRRs they bind pathogen-associated molecular patterns (PAMPs) and also danger-associated molecular patterns (DAMPs) of oligosaccharide origin. Binding of collectins to microorganisms may trigger elimination of microorganisms by aggregation, complement activation, opsonization, activation of phagocytosis or inhibition of microbial growth. Other functions of collectins are modulation of inflammatory, allergic responses, adaptive immune system and clearance of apoptotic cells.

Structure

Functionally collectins are trimers. Monomeric subunit consists of four parts:

• a cysteine-rich domain at the N-terminus
• a collagen-like domain
• a coiled-coil neck domain
• a C-type lectin domain that is also called a carbohydrate recognition domain (CRD)

Recognition of specific parts of microorganism is mediated by CRD in presence of calcium. Affinity of interaction between microbes and collectins depends on the degree of collectin oligomerization and also on the density of ligands on the surface of the microbe.

Types of collectins

9 types of collectins have been defined to date:

• MBL = mannan-binding lectin (mannose-binding lectin)
• SP-A = surfactant protein A
• SP-D = surfactant protein D
• CL-L1 = collectin liver 1
• CL-P1 = collectin placenta 1
• CL-43 = conglutinin collectin of 43 kDa
• CL-46 = collectin of 46 kDa
• CL-K1 = collectin kidney 1
• Conglutinin

CL-43, CL-46 and conglutinin are found in bovine.

Function

Aggregation

Collectins can bind on the surface of the microorganism and between carbohydrate ligands can be made a bond. Due to those properties the interaction can result into aggregation.

Opsonization and activation of phagocytosis

Collectins can act as opsonins. There is a specific interaction between collectins and receptors on phagocytic cells which can lead to increased clearance of microorganisms. MBL can bind to microorganisms and this interaction can lead to opsonization through complement activation, or it can opsonize the microorganism directly. SP-A and SP-D can also interact with microorganisms and phagocytic cells to enhance phagocytosis of the microorganism.

Inhibition of microbial growth

Collectins have effect on microorganism survival. SP-A and SP-D can bind to LPS (lipopolysaccharide) of both Gram-negative and Gram-positive bacteria. SP-A and SP-D can increase permeability of Gram-negative bacterial cell membrane.

Modulation of inflammatory responses

SP-A and SP-D can damp induction of inflammation by LPS or endotoxin. It can be caused by removing the LPS or by binding the LPS to CD14 receptor on macrophages which can block the inflammatory response. SP-A can also bind to TLR2 (Toll-like receptor 2). This interaction causes decrease of TNF-α (Tumor necrosis factor-α) production by alveolar macrophages stimulated with peptidoglycan. SP-A and SP-D can modulate cytokine production. They modulate the production of oxygen and nitrogen reactive species which are very important for phagocytic cells. SP-A and SP-D has s function as chemoattractants for alveolar neutrophils and monocytes. MBL can recognize peptidoglykan via N-acetylglukosamine. This interaction leads to inhibition of ligand-induced inflammatory by macrophage chemokine production.

Modulation of the adaptive immune system

SP-A and SP-D can suppress activated T-lymphocytes and IL-2 (interleukin-2) production. SP-D increases bacterial antigen presentation by dendritic cells whereas SP-A blocs differentation of the immature dendritic cells.

Modulation of allergic response

Collectins SP-A and SP-D have anti-allergic effect. They inhibit IgE binding to allergen, decrease histamin release from basophils and inhibit T-lymfocyte production in the late phase of the inflammation.

Apoptosis

Collectins SP-A and SP-D enhance clearance of apoptotic cells by macrophages.

Complement activation

Collectins are linked with activation of lectin pathway of complement activation. At the beginning, there is a binding of collectin to PAMPs or DAMPs. Collectin MBL is involved in activation of the lectin complement pathway. There are three serine proteases, MASP-1, 2 and 3 (MBL-associated serine proteases), which participate in activation of the lectin pathway. MASP-2 has a cleavage activity and it is essential for forming lectin C3 and C5 convertases and for activation of the complement.

Reviews

For more informations and details see reviews: