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PubMed2000

Collectins and collectin receptors in innate immunity.

This thesis is based on nine papers and a review on the collectins and collectin receptors in innate immunity. The collectins are a family of proteins in which the individual chains consist of a C-type lectin domain attached to a collagen domain via an alpha-coiled neck region. The chains are organized into a triple collagen helix and oligomerized through N-terminally located cysteines. The collectins have a dual function: one is to bind specifically to carbohydrate structures on the surface of a pathogen; the other is subsequently to recruit other cells and molecules to destroy the pathogen. The C-type lectin domains contain 110-130 amino-acid residues arranged in a conserved sequence pattern which allows the domain to fold into a well-defined tertiary structure. Five collectins have been described. Lung surfactant proteins A and D (SP-A and SP-D) are mainly found in the surfactant coating the luminal surface of the pulmonary epithelial cells, but are also produced by cells lining the gastrointestinal tract. Mannan-binding lectin (MBL), conglutinin and collectin-43 (CL-43) are serum proteins produced by the liver. Conglutinin and CL-43 have so far only been found in Bovidae. The collectins are involved in innate, nonadaptive immune defense. They bind to microbial surface carbohydrates, inducing aggregation and thereby impeding infectivity or mediating phagocytosis through specific receptors on the phagocytes. After binding microbial carbohydrate, MBL can activate the complement system through a newly discovered pathway which makes use of two serine proteases (MASP-1 and MASP-2) to activate the complement factors C4 and C2. In man, low serum MBL concentrations resulting from mutations in the collagen region are associated with a common opsonic defect. CL-43 was identified as a new collectin by its calcium-dependent binding to mannan and by its M(r) of 43 kDa in the reduced state on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The lectin was isolated by affinity chromatography on mannan-Sepharose, absorption with rabbit anti-bovine Ig coupled to Sepharose-4B and ion-exchange chromatography. CL-43 shows an apparent molecular mass of 120 kDa in the unreduced state on SDS-PAGE and elutes with an apparent molecular mass of 750 kDa on gel chromatography under nondissociating conditions. Amino-acid analysis and susceptibility to collagenase digestion indicated that CL-43 was a collectin. Electron microscopy of purified CL-43 revealed only rod-like monomer subunits 37.4 nm long. Two-dimensional gel electrophoresis showed that CL-43 has two isoforms of pI 4.9 and 5.3 respectively, corresponding to the native form of CL-43 and a truncated form which lacks the first 9 amino-acid residues. The N-terminal amino-acid sequence of CL-43 was used to design primers for PCR with a bovine liver cDNA as template. The cDNA of CL-43 was cloned and the open reading frame was found to encode a protein of 301 amino-acid residues, including an N-terminal region of 28 residues, a collagen region of 114 residues and a neck-CRD region of 159 residues. The amino-acid sequence of CL-43 shows 74% identity with bovine conglutinin and 70% identity with bovine SP-D, but the collagen region is considerably shorter than those of conglutinin and SP-D. Northern blot analysis showed that CL-43 was only synthesized in bovine liver, no signal being detected in a variety of other bovine tissues, including lung. No cross-hybridizing signals were detected in mRNA from ovine, human, rat or mouse liver. Since CL-43 and conglutinin have only been detected in members of the Bovidae, it is probable that an ancestral gene of these two proteins was first derived from a SP-D-like gene and that this ancestral gene underwent duplication during evolution. The carbohydrate binding profile of CL-43 was analyzed by an inhibition assay with biotinylated CL-43, using solid-phase mannan as the ligand. (ABSTRACT TRUNCATED)

Amino Acid Sequence↗

PubMed1998

Structural aspects of collectins and receptors for collectins.

The collectins are oligomeric molecules composed of C-type lectin domains attached to collagen regions via alpha-coiled neck regions. Five members of the collectins have been characterized. Mannan-binding lectin (MBL), conglutinin and collectin-43 (CL-43) are serum proteins produced by the liver. Lung surfactant protein A (SP-A) and lung surfactant protein D (SP-D) are mainly found in the lung, where they are synthesized by alveolar type II cells and secreted to the alveolar surface. The collectins are believed to play an important role in innate immunity. They bind oligosaccharides on the surface of a variety of microbial pathogens. After binding of the collectins to the microbial surface effector mechanisms such as agglutination, neutralizing or opsonization of the microorganisms for phagocytosis are initiated. SP-A and SP-D stimulate chemotaxis of phagocytes and once bound to the phagocytes, the production of oxygen radicals can be induced. In the case of MBL the opsonization can be further enhanced by complement activation via the MBLectin pathway while conglutinin interacts with the complement system by binding to the complement degradation product iC3b. A number of receptors and binding molecules interacting with the collectins are found on the membrane or in association with the membrane of various cells responsible for phagocytosis and clearance of microorganisms. This paper focus on the structural aspects of the collectins and the receptors for collectins.

Amino Acid Sequence↗

PubMed2006

Alloiococcus otitidis is a ligand for collectins and Toll-like receptor 2, and its phagocytosis is enhanced by collectins.

Alloiococcus otitidis has been found to be associated with otitis media with effusion. In this study we investigated whether TLR2 and collectins, surfactant protein A (SP-A) and mannose-binding lectin (MBL), interacted with A. otitidis. Both SP-A and MBL bound to A. otitidis in a Ca(2+)-dependent manner. A. otitidis induced IL-8 secretion from U937 cells and NF-kappaB activation in TLR2-transfected HEK293 cells. However, the cells transfected with the mutant TLR2(P681H) did not respond to A. otitidis. In addition, A. otitidis co-sedimented a recombinant soluble form of the extracellular TLR2 domain, indicating direct binding of the bacterium to TLR2. SP-A and MBL augmented the phagocytosis of A. otitidis by J774A.1 cells. The collectin-stimulated phagocytosis of A. otitidis was significantly attenuated when fucoidan and polyinosinic acid were co-incubated. Immunoblotting analysis revealed that MBL was present in the middle ear effusion from patients with otitis media. These results demonstrate that A. otitidis is a ligand for the collectins and TLR2, and that the collectins enhance the phagocytosis of A. otitidis by macrophages, suggesting important roles of the collectins and TLR2 in the innate immunity of the middle ear against A. otitidis infection.

Animals↗

PubMed1995

Comparative study of the structural and functional properties of a bovine plasma C-type lectin, collectin-43, with other collectins.

Collectin-43 (CL-43) is a recently described bovine plasma protein containing both collagenous regions and C-type-lectin domains [Holmskov, Teisner, Willis, Reid and Jensenius (1993) J. Biol. Chem. 268, 10120-10125; Lim, Willis, Reid, Lu, Laursen, Jensenius and Holmskov (1994) J. Biol. Chem. 269, 11820-11824]. CL-43 was purified by affinity chromatography on mannan-Sepharose. On SDS/PAGE under reducing conditions the purified lectin showed a double band at about 43 kDa, with the upper band representing the intact molecule and the lower band a truncated form that lacked the N-terminal nine amino acid residues. Under non-reducing conditions, only one band was seen at 120 kDa. Analytical gel chromatography and sucrose-density-gradient centrifugation of the purified molecule, showed a Stokes radius of 9.1 +/- 0.3 nm (91 +/- 3 A) and a sedimentation coefficient (s20,w) of 3.6 +/- 0.1 S. These values correspond to a molecular mass of 119-138 kDa under non-denaturing condition in solution. The frictional coefficient (f/f0) was 2.7, indicating extreme elongation due to the collagenous segment. Only monomer subunits, with 37.4 +/- 1.7-nm-long rods, were seen by electron microscopy. These findings indicate that CL-43, in contrast with the other circulating collectins, is found only as a single subunit composed of three polypeptide chains. Two-dimensional gel electrophoresis showed that CL-43 has two isoforms, with pI values of 4.9 and 5.3, corresponding to the native form and the truncated form of the molecule respectively. CL-43, like conglutinin, lung surfactant protein A and mannan-binding protein (MBP), was shown to bind to the collectin receptor. Bovine MBP caused the activation of the complement system as revealed by the deposition of complement component C4 upon incubation of diluted serum in wells containing MBP bound to solid-phase mannan. CL-43, lung surfactant protein D (SP-D) and conglutinin showed no complement-activating properties under the same conditions. Conglutinin binds fluid- and solid-phase iC3b, while CL-43 and MBP do not show such reactivity.

Animals↗

PubMed1994

Collectins, collectin receptors and the lectin pathway of complement activation.

The collectins are a group of soluble multimeric lectins, which contain collagenous segments, and resemble the complement protein C1q in aspects of their structures and functions. This group of proteins, which includes MBP, SP-A, SP-D, conglutinin and CL-43, are known to act as opsonins in various circumstances, and are likely to have roles in innate immunity. The focus of current research is to pursue the hypothesis that the collectins recognize and bind to non-host carbohydrate structures on microorganisms and particles, and participate in the processing or elimination of such material, either by direct interaction with phagocytic cell receptors, or by indirect routes such as complement activation .

Animals↗

PubMed2005

Characterization and expression sites of newly identified chicken collectins.

Collectins are members of the family of vertebrate C-type lectins. They have been found almost exclusively in mammals, with the exception of chicken MBL. Because of their important role in innate immunity, we sought to identify other collectins in chicken. Using the amino acid sequences of known collectins, the EST database was searched and related to the chicken genome. Three chicken collectins were found and designated chicken Collectin 1 (cCL-1), chicken Collectin 2 (cCL-2), and chicken Collectin 3 (cCL-3), which resemble the mammalian proteins Collectin Liver 1, Collectin 11 and Collectin Placenta 1, respectively. Additionally, a lectin was found which resembled Surfactant Protein A, but lacked the collagen domain. Therefore, it was named chicken Lung Lectin (cLL). Tissue distribution analysis showed cCL-1, cCL-2 and cCL-3 are expressed in a wide range of tissues throughout the digestive, the reproductive and the lymphatic system. Similar to SP-A, cLL is mainly localized in lung tissue. Phylogenetic analysis indicates that cCL-1, cCL-2 and cCL-3 represent new subgroups within the collectin family. The newly found collectins may have an important function in avian host defence. Elucidation of the role of these pattern-recognition molecules could lead to strategies that thwart infectious diseases in poultry, which could also be beneficial for public health.

Amino Acid Sequence↗

PubMed1999

Molecular cloning of a novel human collectin from liver (CL-L1).

Collectins are a C-lectin family with collagen-like sequences and carbohydrate recognition domains. These proteins can bind to carbohydrate antigens of microorganisms and inhibit their infection by direct neutralization and agglutination, the activation of complement through the lectin pathway, and opsonization by collectin receptors. Here we report the cloning of a cDNA encoding human collectin from liver (CL-L1 (collectin liver 1)) that has typical collectin structural characteristics, consisting of an N-terminal cysteine-rich domain, a collagen-like domain, a neck domain, and a carbohydrate recognition domain. The cDNA has an insert of 831 base pairs coding for a protein of 277 amino acid residues. The deduced amino acid sequence shows that this collectin has a unique repeat of four lysine residues in its C-terminal area. Northern blot, Western blot, and reverse transcription-polymerase chain reaction analyses showed that CL-L1 is present mainly in liver as a cytosolic protein and at low levels in placenta. More sensitive analyses by reverse transcription-polymerase chain reactions showed that most tissues (except skeletal muscle) have CL-L1 mRNA. Zoo-blot analysis indicated that CL-L1 is limited to mammals and birds. A chromosomal localization study indicated that the CL-L1 gene localizes to chromosome 8q23-q24.1, different from chromosome 10 of other human collectin genes. Expression studies of fusion proteins lacking the collagen and N-terminal domains produced in Escherichia coli affirmed that CL-L1 binds mannose weakly. CL-L1 and recombinant CL-L1 fusion proteins do not bind to mannan columns. Analysis of the phylogenetic tree of CL-L1 and other collectins indicated that CL-L1 belongs to a fourth subfamily of collectins following the mannan-binding protein, surfactant protein A, and surfactant protein D subfamilies including bovine conglutinin and collectin-43 (CL-43). These findings indicate that CL-L1 may be involved in different biological functions.

Amino Acid Sequence↗

PubMed1993

Similarity in structure between C1q and the collectins as judged by electron microscopy.

The collectins are carbohydrate binding proteins which, like C1q, contain collagen-like sequences. The collectins belong to group III of the family of lectins containing C-type carbohydrate recognition domains (CRDs). The structural similarity between the collectins and C1q is clearly demonstrated by electron microscopy in that they all contain multiple polypeptides which are organised into subunits containing triple-helical stalks throughout their collagen-like regions and globular 'heads' in the C-terminal regions. Four, or six, of these structures are associated via distinct, short, N-terminal regions to form the oligomeric molecules seen in the electron microscope. The overall structural similarity between C1q and the collectins, however, does not extend to similarity in amino acid sequences over the C-terminal regions. The C-terminal regions of C1q, unlike those of the collectins, do not contain the conserved residues found in the CRDs present in the C-type lectins. Instead, C1q has a high degree of homology to collagen sequences (Type VIII and X) and this is consistent with the fact that, unlike the collectins, C1q binds to protein motifs in IgG, or IgM, rather than to carbohydrate structures. Also, despite sometimes showing interruptions in their collagen-like regions, the collectins do not always display a 'bend' in their collagen-like 'stalks' similar to that which is seen in C1q. Therefore, C1q may be more closely related to collagens than to the collectins. The collectins can be classed into two distinct group, with MBP and SP-A being hexamers and SP-D, conglutinin and collectin-43 (CL-43) being tetramers, with proteins in the latter group also having significantly larger dimensions with respect to the length of their collagen-like 'stalks'.

Amino Acid Sequence↗

PubMed2004

The genes encoding bovine SP-A, SP-D, MBL-A, conglutinin, CL-43 and CL-46 form a distinct collectin locus on Bos taurus chromosome 28 (BTA28) at position q.1.8-1.9.

Collectins are a group of C-type lectins involved in the innate immune system, where they mediate and modulate clearance of pathogens. The health status of cattle is of major economical and ethical concern; therefore, the study of bovine collectins is of importance. The collectins conglutinin, CL-43 and CL-46 are only present in Bovidae and the characterization of their genes indicates that they are structural descendants of another collectin, lung surfactant protein D (SP-D). In this study, we assembled BAC clones into a contig spanning 330-1150 kb, which includes the bovine genes encoding the collectins SP-A (SFTPA), SP-D (SFTPD), mannan-binding lectin A (MBL1), CL-43 (COLEC9), CL-46 (COLEC13) and conglutinin (COLEC8). In the same contig, we also identified a gene that potentially encodes a novel conglutinin-like collectin (COLEC14). The arrangement of STFPA, SFTPD and MBL1 is homologous to the organization found in humans and mice, whereas the Bovidae-specific collectin genes, COLEC8, COLEC9 and COLEC13, extend from SFTPD. Proximal to the collectin locus at BTA28q1.8-1.9, and included in the contig, we found the microsatellite IDVGA8, which may be a valuable marker for tracking polymorphisms in the linked collectin genes.

Amino Acid Sequence↗

PubMed2003

Secretion of a collectin-like protein in tunicates is enhanced during inflammatory responses.

The sub-cellular and humoral concentrations of a collectin-like protein from the solitary tunicate, Styela plicata, were measured after in vivo challenge with the inflammatory agent, zymosan. Tunicates were injected with zymosan before hemocytes and serum were harvested, subjected to western blotting and immunostained with an anti-S. plicata collectin antibody to determine the relative titers of collectin-like proteins. Concentrations of the predominant 43kDa collectin polypeptide were found to decrease in hemocytes immediately after zymosan injection, before rising to levels that were six times higher than controls within 96h. Similarly, immunohistochemistry showed that the frequency of collectin-positive hemocytes in the circulating hemolymph increased significantly within 96h of injection. Levels of the 43kDa polypeptide in serum mirrored those of hemocytes. Humoral collectin concentrations decreased immediately after zymosan injection before rising, within 96h post-injection, to levels three times higher than controls. This response to an inflammatory stimulus resembles that of mammalian collectins like mannose-binding lectin. The data suggest that, like its mammalian counterparts, the tunicate collectin acts as an acute phase antigen recognition protein.

Animals↗

PubMed1998

Antiviral activity of bovine collectins against rotaviruses.

The antiviral activity against rotaviruses of three bovine collectins, conglutinin, collectin-43 (CL-43) and bovine SP-D, was examined. As shown by ELISA and Western blot, all three collectins bound to the Nebraska calf diarrhoea virus bovine strain of rotavirus, and specifically to the VP7 glycoprotein. Inhibition by mannose or EDTA confirmed that binding was mediated through the lectin domains of the collectins. Binding resulted in haemagglutination inhibition and neutralization of rotavirus infectivity, CL-43 displaying the highest activity in both types of assay. In contrast, conglutinin was the most potent of the three collectins against influenza virus A/HKx31. Neutralization of rotaviruses by the lectins was dependent on glycosylation of VP7. Furthermore, rotaviruses adapted to growth in Madin-Darby bovine kidney cells, and thus bearing carbohydrate of bovine origin, remained sensitive to neutralization, although slightly less so than virus stocks propagated in the monkey kidney cell line MA104. These findings provide the first description of antiviral activity of collectins against a non-enveloped virus and may indicate a potential role for collectins in host defence against bovine rotavirus infection.

Animals↗

PubMed2004

Collectins: players of the innate immune system.

Collectins are a family of collagenous calcium-dependent defense lectins in animals. Their polypeptide chains consist of four regions: a cysteine-rich N-terminal domain, a collagen-like region, an alpha-helical coiled-coil neck domain and a C-terminal lectin or carbohydrate-recognition domain. These polypeptide chains form trimers that may assemble into larger oligomers. The best studied family members are the mannan-binding lectin, which is secreted into the blood by the liver, and the surfactant proteins A and D, which are secreted into the pulmonary alveolar and airway lining fluid. The collectins represent an important group of pattern recognition molecules, which bind to oligosaccharide structures and/or lipid moities on the surface of microorganisms. They bind preferentially to monosaccharide units of the mannose type, which present two vicinal hydroxyl groups in an equatorial position. High-affinity interactions between collectins and microorganisms depend, on the one hand, on the high density of the carbohydrate ligands on the microbial surface, and on the other, on the degree of oligomerization of the collectin. Apart from binding to microorganisms, the collectins can interact with receptors on host cells. Binding of collectins to microorganisms may facilitate microbial clearance through aggregation, complement activation, opsonization and activation of phagocytosis, and inhibition of microbial growth. In addition, the collectins can modulate inflammatory and allergic responses, affect apoptotic cell clearance and modulate the adaptive immune system.

Animals↗

PubMed1994

Mannan-binding protein levels in human amniotic fluid during gestation and its interaction with collectin receptor from amnion cells.

Collectins are a group of soluble proteins, each of which has collagenous and non-collagenous globular domains, and may be complement associated and/or have lectin activity. The complement protein C1q is structurally and functionally related to the collectins. Members of the collectin family are mannan-binding protein (MBP), lung surfactant protein A, CL-43, conglutinin and lung surfactant protein D. All except the last of these proteins have been shown to interact with a single, widely distributed receptor, named collectin receptor (also called C1q receptor). It has been proposed that collectins play an important role as opsonins in innate immunity. MBP is a serum protein and has been shown to activate the classical complement pathway. MBP has also been shown to opsonize bacteria and enhance clearance of bacteria by phagocytosis. In this article we demonstrate the presence of MBP in amniotic fluid and the localization of collectin receptor on the surface of amniotic epithelium. MBP levels in amniotic fluid were found to increase sharply from about 32 weeks of gestation. Collectin receptor was purified from a cell line, FL, derived from amniotic epithelium and was shown to interact with MBP. These results suggest that MBP may play a role in the antibody-independent recognition and clearance of pathogens in the amniotic cavity, towards term.

Amino Acid Sequence↗

PubMed2004

Nucleic acid is a novel ligand for innate, immune pattern recognition collectins surfactant proteins A and D and mannose-binding lectin.

Collectins are a family of innate immune proteins that contain fibrillar collagen-like regions and globular carbohydrate recognition domains (CRDs). The CRDs of these proteins recognize various microbial surface-specific carbohydrate patterns, particularly hexoses. We hypothesized that collectins, such as pulmonary surfactant proteins (SPs) SP-A and SP-D and serum protein mannose-binding lectin, could recognize nucleic acids, pentose-based anionic phosphate polymers. Here we show that collectins bind DNA from a variety of origins, including bacteria, mice, and synthetic oligonucleotides. Pentoses, such as arabinose, ribose, and deoxyribose, inhibit the interaction between SP-D and mannan, one of the well-studied hexose ligands for SP-D, and biologically relevant d-forms of the pentoses are better competitors than the l-forms. In addition, DNA and RNA polymer-related compounds, such as nucleotide diphosphates and triphosphates, also inhibit the carbohydrate binding ability of SP-D, or approximately 60 kDa trimeric recombinant fragments of SP-D that are composed of the alpha-helical coiled-coil neck region and three CRDs (SP-D(n/CRD)) or SP-D(n/CRD) with eight GXY repeats (SPD(GXY)(8)(n/CRD)). Direct binding and competition studies suggest that collectins bind nucleic acid via their CRDs as well as by their collagen-like regions, and that SP-D binds DNA more effectively than do SP-A and mannose-binding lectin at physiological salt conditions. Furthermore, the SP-D(GXY)(8)(n/CRD) fragments co-localize with DNA, and the protein competes the interaction between propidium iodide, a DNA-binding dye, and apoptotic cells. In conclusion, we show that collectins are a new class of proteins that bind free DNA and the DNA present on apoptotic cells by both their globular CRDs and collagen-like regions. Collectins may therefore play an important role in decreasing the inflammation caused by DNA in lungs and other tissues.

Animals↗

PubMed2006

Conglutinin, CL-43 and CL-46--three bovine collectins.

Conglutinin, collectin-43 (CL-43) and collectin-46 (CL-46) are serum proteins characteristic for Bovidae. They belong to collectins--family of oligomeric proteins composed of trimeric subunits containing collagen-like sequences joined to C-type lectin domains. The genes encoding conglutinin, CL-43 and CL-46 are located on the bovine chromosome 28, and phylogenetic analysis indicates their common origin--from the lung surfactant protein D gene. Northern blot or immunocytochemical analysis confirm biosynthesis of bovine collectins mainly in the liver (conglutinin, CL-43) and in the thymus (CL-46). The level of conglutinin in the serum of dairy cows depends on many factors such as breeding, the season of the year, the stage of the reproductive cycle and infection. The collectins are involved in the innate immune defense. They bind to microbial surface carbohydrates inducing aggregation and, thereby, impeding infectivity. On the other hand the destruction of pathogens occurs due to stimulation of effector cells. CL-43 as well as conglutinin, binds to the collectin receptor (C1qR) localized on many types of cells identified as a surface variant of calreticulin. Conglutinin and CL-43 show antiviral activities towards influenza A virus and rotaviruses. Conglutinin also displays protective activity against bacterial infections.

Animals↗

PubMed1993

Structure and function of collectins: humoral C-type lectins with collagenous regions.

Collectins are a family of C-type lectins with collagenous regions. Five such lectins have now been described: Lung surfactant protein A and D (SP-A and SP-D), and the plasma proteins, conglutinin, mannan-binding protein (MBP), and CL-43. They are composed of trimeric subunits containing a collagenous section and a C-terminal globular carbohydrate-recognizing domain containing the 14 invariant amino acids characteristic of the C-type lectins. The complete molecules of MBP and SP-A are composed of up to six such subunits, while conglutinin, SP-D and CL-43 contain up to four subunits. The collectins bind to carbohydrates on yeast, bacteria and viruses. The collagenous section reacts with the C1q receptor (collectin receptor) found on many cells including phagocytes. One function of these lectins appears to be the enhancement of phagocytosis, i.e. opsonization. One of the collectins, mannan-binding protein, activates the C1r2C1s2 complex of the classical complement pathway independently of C1q. Collectins have been found in several mammalian species and in the chicken. It seems likely that the biological role of the collectins is to participate in the innate immune defense.

Amino Acid Sequence↗

PubMed2006

Regulation of inflammation and bacterial clearance by lung collectins.

Pulmonary surfactant proteins (SP) A and D play important roles in the innate immune system of the lung. These proteins belong to the collectin subgroup in which lectin domains are associated with collagenous structures. To obtain a better understanding of how lung collectins modulate cellular responses, the authors investigated whether SP-A interacts with the toll-like receptor 2 (TLR2). SP-A bound to TLR2 and inhibited interactions between TLR2 and TLR2-ligands such as peptidoglycan (PGN) and zymosan. NF-kappaB activation and tumour necrosis factor-alpha expression induced by PGN or zymosan were significantly inhibited in the presence of SP-A. Lung collectins may act as inhibitors of lung inflammation in respiratory infections. The authors also examined the effects of lung collectins on the phagocytosis of bacteria by alveolar macrophages. Lung collectins enhanced the uptake of S. pneumoniae or M. avium by alveolar macrophages. It was demonstrated that the direct interaction of lung collectins with macrophages resulted in increased cell surface expression of scavenger receptor A or mannose receptor, which are responsible for phagocytosis. This study has emphasized the biological relevance of SP-A and SP-D against various respiratory infections, however, a more complete understanding of the molecular mechanism is required.

Animals↗

PubMed1997

Collectins: collectors of microorganisms for the innate immune system.

Collectins are a group of multimeric proteins mostly consisting of 9-18 polypeptides organised into either 'bundle-of-tulips' or 'X-like' overall structures. Each polypeptide contains a short N-terminal segment followed by a collagen-like sequence and then by a C-terminal lectin domain. A collectin molecule is assembled from identical or very similar polypeptides by disulphide bonds at the N-terminal segment, formation of triple helices in the collagen-like region and clusters of three lectin domains at the peripheral ends of triple helices. These proteins can bind to sugar residues on microorganisms via the peripheral lectin domains and subsequently interact, via the collagen-like triple-helices, with receptor(s) on phagocytes and/or the complement system to bring about the killing and clearance of the targets without the involvement of antibodies. The collectins can also bind to phagocyte receptor(s) to enhance phagocytosis mediated by other phagocytic receptors. Lack, or low levels, of collectin expression can lead to higher susceptibility to infections, especially during childhood when specific immunity has not fully developed. Therefore, the collectins play important roles in the enhancement of innate immunity.

Animals↗