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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↗
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↗
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↗
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↗
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↗
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↗
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↗
PubMed2001

The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells.

Collectins are a family of C-type lectins that have collagen-like sequences and carbohydrate recognition domains (CRD). They are involved in host defense through their ability to bind to carbohydrate antigens of microorganisms. The scavenger receptors type A and MARCO are classical type scavenger receptors that have internal collagen-like domains. Here we describe a new scavenger receptor that is a membrane-type collectin from placenta (collectin placenta 1 (CL-P1)), which has a typical collectin collagen-like domain and a CRD. The cDNA has an insert of about 2.2 kilobases coding for a protein containing 742 amino acid residues. The deduced amino acid sequence shows that CL-P1 is a type II membrane protein, has a coiled-coil region, a collagen-like domain, and a CRD. It resembles type A scavenger receptors because the scavenger receptor cysteine-rich domain is replaced by a CRD. Northern analyses, reverse transcription-polymerase chain reaction, and immunohistochemistry show that CL-P1 is expressed in vascular endothelial cells but not in macrophages. By immunoblotting and flow cytometry CL-P1 appears to be a membrane glycoprotein of about 140 kDa in human umbilical vein or arterial endothelial cells, placental membrane extracts, and CL-P1 transfected Chinese hamster ovary cells. We found that CL-P1 can bind and phagocytose not only bacteria (Escherichia coli and Staphylococcus aureus) but also yeast (Saccharomyces cerevisiae). Furthermore, it reacts with oxidized low density lipoprotein (OxLDL) but not with acetylated LDL (AcLDL). These binding activities are inhibited by polyanionic ligands (polyinosinic acid, polyguanylic acid, dextran sulfate) and OxLDL but not by polycationic ligands (polyadenylic acid or polycytidylic acid), LDL, or AcLDL. These results indicate that CL-P1 might play important roles in host defenses that are different from those of soluble collectins in innate immunity.

Amino Acid Sequence↗
PubMed1995

Collectin-43 is a serum lectin with a distinct pattern of carbohydrate recognition.

Collectin-43 (CL-43) is a C-type serum lectin and a member of the collectin family of soluble proteins that are effector molecules in innate immunity. We have investigated the binding specificity of CL-43 using as model systems a panel of structurally defined oligosaccharides in the form of neoglycolipids, and several glycoproteins derived from the complement glycoprotein C3 during activation of the complement cascade. A specificity is revealed towards fucose as part of the Lea oligosaccharide sequence, and towards mannose as found on high mannose-type chains. These are features shared with other serum collectins, conglutinin and mannan-binding proteins; a major difference is the lack of detectable binding by CL-43 to N-glycosidic oligosaccharides terminating in N-acetylglucosamine. CL-43 has a unique pattern of reactivity towards high mannose-type oligosaccharides on the two glycosylation sites of C3 and derived glycoproteins: it binds to C3c (not bound by conglutinin and mannan-binding protein) but not to hydrolysed C3 [C3(H2O)], C3b or iC3b immobilized on microwells (all bound by conglutinin but not by mannan-binding protein). When these glycoproteins are sodium dodecyl sulphate (SDS)-treated and immobilized on nitrocellulose, CL-43 (but not conglutinin nor mannan-binding protein) binds strongly to C3(H2O), iC3b and C3c. The salient conclusions are, first, that there are remarkable positive or negative effects of carrier protein on oligosaccharide presentation and these differ for the individual collectins. Second, the different though partially overlapping binding patterns among the collectins may be important for their function as circulating effector molecules with broad surveillance capabilities.

Animals↗
PubMed1994

Collectins--soluble proteins containing collagenous regions and lectin domains--and their roles in innate immunity.

The collectins are a group of mammalian lectins containing collagen-like regions. They include mannan binding protein, bovine conglutinin, lung surfactant protein A, lung surfactant protein D, and a newly discovered bovine protein named collectin-43. These proteins share a very similar modular domain composition and overall 3-dimensional structure. They also appear to play similar biological roles in the preimmune defense against micro-organisms in both serum and lung surfactant. The close evolutionary relationship between the collectins is further emphasized by a common pattern of exons in their genomic structures and the presence of a gene cluster on chromosome 10 in humans that contains the genes known for the human collectins. Studies on the structure/function relationships within the collectins could provide insight into the properties of a growing number of proteins also containing collagenous regions such as C1q, the hibernation protein, the alpha- and beta-ficolins, as well as the membrane acetylcholinesterase and the macrophage scavenger receptor.

Amino Acid Sequence↗
PubMed2000

A collectin-like protein from tunicates.

Collectins are a sub-family of C-type lectins from mammals and birds that are characterized by their collagen-like domains. The mammalian collectin, mannose binding lectin, has attracted considerable interest because it can activate complement components via a lectin-mediated complement pathway that is independent of immunoglobulins. In this study, we have identified a calcium-dependent lectin from the invertebrate (tunicate), Styela plicata, that bears substantial similarities to mammalian collectins. The tunicate lectin, which was isolated by carbohydrate affinity chromatography, has a reduced apparent molecular mass of 43 kDa. The 43 kDa reduced polypeptide appeared as dimers, trimers and hexamers when analyzed by non-reducing and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while gel filtration suggested that the native form of the protein was a nonamer. Amino acid sequence and amino acid composition analysis revealed obvious similarities between the tunicate lectin and mammalian collectins, notably the inclusion of a collagenous domain and a short, cysteine bearing N-terminal domain. The identification of a collectin-like protein in an invertebrate such as S. plicata, which does not express immunoglobulin, indicates that lectin-mediated complement pathways may predate the origin of antibodies.

Amino Acid Sequence↗
PubMed1995

Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells.

Cryptococcus neoformans is an opportunistic pathogen in AIDS patients causing disseminated disease and lethal meningitis after inhalation of acapsular or sparsely encapsulated yeast cells. In this study we have investigated whether a recently described family of primitive opsonins, termed collectins, contribute to innate resistance against C. neoformans. The pulmonary surfactant proteins SP-A and SP-D as well as the serum collectins mannose-binding protein and CL-43 bound in a calcium-dependent manner to acapsular C. neoformans in vitro. Binding was concentration dependent and abolished by competition with defined mono- and oligosaccharides. In contrast, no binding of the collectins was observed with the encapsulated form of the yeast. Furthermore, binding of purified collectin SP-D, but not SP-A, mannose-binding protein, or CL-43, led to a concentration-dependent agglutination of acapsular C. neoformans. These data indicate that collectins recognize carbohydrate structures in the cell wall of an initial infectious form of C. neoformans and may play a role in early antifungal defenses in the lung.

Agglutinins↗
PubMed1996

Affinity and kinetic analysis of the bovine plasma C-type lectin collectin-43 (CL-43) interacting with mannan.

Collectins are C-type lectins which have been implied to play an important role in the innate immune defence against microorganisms. The critical discriminatory event in the opsonization of microorganisms by collectins is the interaction of the C-type lectin domain with microbial carbohydrates. Surface plasmon resonance measurements allow for quantitative real-time measurements of binding interaction between immobilized carbohydrate and unlabelled lectin in solution. Binding analysis were carried out with purified collectin-43 (CL-43) which structurally is the simplest collectin consisting of only three polypeptides each terminating in a C-type lectin domain. The target was immobilized yeast mannan. The molecular mass of native CL-43 was determinated by mass spectroscopy to 99.8 kDa. The dissociation rate (kdiss) of the C-type lectin-carbohydrate binding was fast (1.19-1.36 x 10(-2) second-1), and the association rate (kass) was 4.37-5.07 x 10(5) M-1 second-1. The equilibrium constant for dissociation (Kd) was 2.68-2.72 x 10(-8) M.

Animals↗
PubMed2001

Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D.

Surfactant proteins SP-A and SP-D, members of the collectin family, have been shown to play a significant role in lung host defense. Both proteins selectively bind Pneumocystis carinii (PC) organisms and modulate the interaction of this pathogen with alveolar macrophages. We hypothesized that the expression and distribution of lung collectins SP-A and SP-D is altered by PC lung infection. PC organisms (2 x 10(5)) were inoculated intratracheally into C.B-17 scid/scid mice that do not require steroids for immunosuppression. Four weeks after inoculation, bronchoalveolar lavage (BAL) fluid was fractionated into three fractions-cell pellet, large aggregate (LA), and small aggregate (SA) surfactant-and each fraction was analyzed for the expression of surfactant components. In uninfected mice, the majority of SP-A (62% +/- 10%) was found in association with lipids in the LA fraction, while 55% +/- 14% of SP-D was distributed in the SA fraction. In contrast, both hydrophobic proteins SP-B and SP-C were associated exclusively with LA. PC infection resulted in major changes in the expression of all surfactant components. Total protein content of LA was unchanged by PC infection (115% +/- 18% of control), whereas SA protein content markedly increased (240% +/- 18% of control level, P <.001). In contrast, the phospholipid content of LA was significantly decreased (53% +/- 5% of control level, P <.001), whereas the SA phospholipid content of infected mice was increased (172% +/- 16% of control level, P <.001). By Western blotting, PC pneumonia (PCP) induced a 3-fold increase in the total alveolar SP-D protein that was reflected mainly in increases in SA SP-D (454% +/- 135% of control, P <.05). The total alveolar SP-A protein content was also increased in PCP because of a large increase in SP-A in SA (720% +/- 115% of control, P <.05); SP-A levels in LA were unchanged. The increases in lung collectin expression were selective, because PCP resulted in the down-regulation of both SP-B and SP-C in LA (5% +/- 2% and 13% +/- 2% of control, respectively, P <.001). We conclude that PCP induces marked elevations in alveolar collectin levels because of increased expression and accumulation of SP-A and SP-D protein in SA surfactant.

Animals↗
PubMed2000

Collectin structure: a review.

Collectins are animal calcium dependent lectins that target the carbohydrate structures on invading pathogens, resulting in the agglutination and enhanced clearance of the microorganism. These proteins form trimers that may assemble into larger oligomers. Each polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen like region, an alpha-helical coiled-coil, and the lectin domain. Only primary structure data are available for the N-terminal region, while the most important features of the collagen-like region can be derived from its homology with collagen. The structures of the alpha-helical coiled-coil and the lectin domain are known from crystallographic studies of mannan binding protein (MBP) and lung surfactant protein D (SP-D). Carbohydrate binding has been structurally characterized in several complexes between MBP and carbohydrate; all indicate that the major interaction between carbohydrate and collectin is the binding of two adjacent carbohydrate hydroxyl group to a collectin calcium ion. In addition, these hydroxyl groups hydrogen bond to some of the calcium amino acid ligands. While each collectin trimer contains three such carbohydrate binding sites, deviation from the overall threefold symmetry has been demonstrated for SP-D, which may influence its binding properties. The protein surface between the three binding sites is positively charged in both MBP and SP-D.

Amino Acid Sequence↗