{{Short description|Part of the innate immune system}} '''Collectins''', col-lectins, ('''collagen-containing C-type lectins''') are a part of the innate immune system. They form a sub-family of collagenous Ca<sup>2+</sup>-dependent lectins of the family of C-type lectins, which are found in animals. Collectins are soluble pattern recognition receptors (PRRs). Their function is to bind to oligosaccharide structure or lipids that are on the surface of microorganisms. Like other PRRs they bind pathogen-associated molecular patterns (PAMPs) and damage-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.<ref>{{Cite journal | issn = 0021-9258| volume = 266| issue = 31| pages = 20678–20686| last = Weis| first = W I|author2=G V Crichlow |author3=H M Murthy |author4=W A Hendrickson |author5=K Drickamer | title = Physical characterization and crystallization of the carbohydrate-recognition domain of a mannose-binding protein from rat| journal = The Journal of Biological Chemistry| date = 1991-11-05| doi = 10.1016/S0021-9258(18)54762-1| pmid = 1939118| doi-access = free}}</ref><ref>{{Cite journal| doi = 10.1038/360127a0| pmid = 1436090| issn = 0028-0836| volume = 360| issue = 6400| pages = 127–134| last = Weis| first = W I|author2=K Drickamer |author3=W A Hendrickson | title = Structure of a C-type mannose-binding protein complexed with an oligosaccharide| journal = Nature| date = 1992-11-12| bibcode = 1992Natur.360..127W| s2cid = 4353217}}</ref> 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.<ref>{{Cite journal| issn = 0021-9258| volume = 266| issue = 8| pages = 4810–4815| last = Lee| first = R T|author2=Y Ichikawa |author3=M Fay |author4=K Drickamer |author5=M C Shao |author6=Y C Lee | title = Ligand-binding characteristics of rat serum-type mannose-binding protein (MBP-A). Homology of binding site architecture with mammalian and chicken hepatic lectins | journal = The Journal of Biological Chemistry| date = 1991-03-15| doi = 10.1016/S0021-9258(19)67721-5| pmid = 2002028| doi-access = free}}</ref>
==Types of collectins== Nine types of collectins have been defined: *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 = Collectin of 43 kDa *CL-46 = collectin of 46 kDa *CL-K1 = collectin kidney 1 *Conglutinin<ref>{{MeshName|conglutinin}}</ref>
CL-43, CL-46 and conglutinin are found in bovines.
==Function==
===Aggregation=== Collectins can bind to the surface of microorganisms and between carbohydrate ligands. Due to these properties, the interaction can result in aggregation.<ref>{{Cite journal| issn = 0022-1767| volume = 163| issue = 1| pages = 312–321| last = Ferguson| first = J S|author2=D R Voelker |author3=F X McCormack |author4=L S Schlesinger | title = Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reducedphagocytosis of the bacteria by macrophages| journal = Journal of Immunology | date = 1999-07-01| doi = 10.4049/jimmunol.163.1.312| s2cid = 86321161| doi-access = free}}</ref><ref>{{Cite journal| issn = 0019-9567| volume = 63| issue=9| pages = 3360–3366| last = Schelenz| first = S|author2=R Malhotra |author3=R B Sim |author4=U Holmskov |author5=G J Bancroft | title = Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells| journal = Infection and Immunity| date = September 1995| doi = 10.1128/IAI.63.9.3360-3366.1995| pmid = 7642263| pmc = 173462}}</ref>
===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.<ref>{{Cite journal| issn = 1044-1549| volume = 11| issue = 1| pages = 114–122| last = McNeely| first = T B|author2=J D Coonrod| title = Aggregation and opsonization of type A but not type B Hemophilus influenzae by surfactant protein A| journal = American Journal of Respiratory Cell and Molecular Biology| date = July 1994| doi=10.1165/ajrcmb.11.1.8018334| pmid = 8018334}}</ref><ref>{{Cite journal| doi = 10.1172/JCI117972| issn = 0021-9738| volume = 95| issue = 6| pages = 2699–2710| last = O'Riordan| first = D M|author2=J E Standing |author3=K Y Kwon |author4=D Chang |author5=E C Crouch |author-link5=Erika Crouch|author6=A H Limper | title = Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophages| journal = The Journal of Clinical Investigation| date = June 1995 | pmid=7769109 | pmc=295953}}</ref><ref>{{Cite journal| doi = 10.1128/IAI.69.1.24-33.2001| pmid = 11119485| pmc = 97851| issn = 0019-9567| volume = 69| issue = 1| pages = 24–33| last = Ofek| first = I|author2=A Mesika |author3=M Kalina |author4=Y Keisari |author5=R Podschun |author6=H Sahly |author7=D Chang |author8=D McGregor |author9=E Crouch | title = Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae| journal = Infection and Immunity| date = January 2001}}</ref> MBL can bind to microorganisms and this interaction can lead to opsonization through complement activation,<ref>{{Cite journal| doi = 10.1146/annurev.immunol.21.120601.140954| issn = 0732-0582| volume = 21| pages = 547–578| last = Holmskov| first = Uffe|author2=Steffen Thiel |author3=Jens C Jensenius | title = Collections and ficolins: humoral lectins of the innate immune defense| journal = Annual Review of Immunology| year = 2003| pmid=12524383 }}</ref> or it can opsonize the microorganism directly.<ref>{{Cite journal| issn = 0022-1007| volume = 169| issue = 5| pages = 1733–1745| last = Kuhlman| first = M|author2=K Joiner |author3=R A Ezekowitz | title = The human mannose-binding protein functions as an opsonin| journal = The Journal of Experimental Medicine| date = 1989-05-01| doi=10.1084/jem.169.5.1733| pmid = 2469767| pmc = 2189296}}</ref> SP-A and SP-D can also interact with microorganisms and phagocytic cells to enhance phagocytosis of the microorganism.<ref>{{Cite journal| issn = 0002-9513| volume = 274| issue = 6 Pt 1| pages = L958–969| last = Hartshorn| first = K L|author2=E Crouch |author3=M R White |author4=M L Colamussi |author5=A Kakkanatt |author6=B Tauber |author7=V Shepherd |author8=K N Sastry | title = Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria| journal = The American Journal of Physiology| date = June 1998| pmid = 9609735 | doi = 10.1152/ajplung.1998.274.6.L958}}</ref>
===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.<ref>{{Cite journal| doi = 10.1172/JCI16889| issn = 0021-9738| volume = 111| issue = 10| pages = 1589–1602| last = Wu| first = Huixing |author2=Alexander Kuzmenko |author3=Sijue Wan |author4=Lyndsay Schaffer |author5=Alison Weiss |author6=James H Fisher |author7=Kwang Sik Kim |author8=Francis X McCormack | title = Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability| journal = The Journal of Clinical Investigation|date=May 2003| pmid=12750409 | pmc=155045}}</ref>
===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 that can block the inflammatory response.<ref>{{Cite journal| issn = 0006-3002| volume = 1454| issue = 3| pages = 261–269| last = van Rozendaal| first = B A |author2=C H van de Lest |author3=M van Eijk |author4=L M van Golde |author5=W F Voorhout |author6=H P van Helden |author7=H P Haagsman | title = Aerosolized endotoxin is immediately bound by pulmonary surfactant protein D in vivo| journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease| date = 1999-08-30| doi=10.1016/s0925-4439(99)00042-3| pmid = 10452960| doi-access = free}}</ref><ref>{{Cite journal| issn = 1040-0605| volume = 278| issue = 4| pages = L840–847| last = Borron| first = P|author2=J C McIntosh |author3=T R Korfhagen |author4=J A Whitsett |author5=J Taylor |author6=J R Wright | title = Surfactant-associated protein A inhibits LPS-induced cytokine and nitric oxide production in vivo| journal = American Journal of Physiology. Lung Cellular and Molecular Physiology|date=April 2000| doi = 10.1152/ajplung.2000.278.4.l840 | pmid = 10749762| s2cid = 25269338}}</ref><ref>{{Cite journal| doi = 10.1074/jbc.M001107200| issn = 0021-9258| volume = 275| issue = 29| pages = 22442–22451| last = Sano| first = H|author2=H Chiba |author3=D Iwaki |author4=H Sohma |author5=D R Voelker |author6=Y Kuroki | title = Surfactant proteins A and D bind CD14 by different mechanisms| journal = The Journal of Biological Chemistry| date = 2000-07-21 | pmid=10801802| doi-access = free}}</ref> 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.<ref>{{Cite journal| doi = 10.1074/jbc.M106671200| issn = 0021-9258| volume = 277| issue = 9| pages = 6830–6837| last = Murakami| first = Seiji|author2=Daisuke Iwaki |author3=Hiroaki Mitsuzawa |author4=Hitomi Sano |author5=Hiroki Takahashi |author6=Dennis R Voelker |author7=Toyoaki Akino |author8=Yoshio Kuroki | title = Surfactant protein A inhibits peptidoglycan-induced tumor necrosis factor-alpha secretion in U937 cells and alveolar macrophages by direct interaction with toll-like receptor 2| journal = The Journal of Biological Chemistry| date = 2002-03-01 | pmid=11724772| doi-access = free}}</ref> 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.<ref>{{Cite journal| issn = 0006-3002| volume = 1408| issue = 2–3| pages = 241–263| last = Tino| first = M J|author2=J R Wright| title = Interactions of surfactant protein A with epithelial cells and phagocytes| journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease| date = 1998-11-19| doi=10.1016/s0925-4439(98)00071-4| pmid = 9813349| doi-access = free}}</ref><ref>{{Cite journal| issn = 0031-9333| volume = 77| issue = 4| pages = 931–962| last = Wright| first = J R| title = Immunomodulatory functions of surfactant| journal = Physiological Reviews| date = October 1997| doi=10.1152/physrev.1997.77.4.931| pmid = 9354809}}</ref><ref>{{Cite journal| doi = 10.1146/annurev.physiol.63.1.521| issn = 0066-4278| volume = 63| pages = 521–554| last = Crouch| first = E|author2=J R Wright| title = Surfactant proteins a and d and pulmonary host defense| journal = Annual Review of Physiology| year = 2001| pmid=11181966}}</ref> SP-A and SP-D has s function as chemoattractants for alveolar neutrophils and monocytes.<ref>{{Cite journal| issn = 0002-9513| volume = 276| issue = 1 Pt 1| pages = L164–174| last = Tino| first = M J|author2=J R Wright| title = Surfactant proteins A and D specifically stimulate directed actin-based responses in alveolar macrophages| journal = The American Journal of Physiology| date = January 1999| doi = 10.1152/ajplung.1999.276.1.L164| pmid = 9887069}}</ref> MBL can recognize peptidoglycan via N-acetylglucosamine. This interaction leads to inhibition of ligand-induced inflammatory by macrophage chemokine production.<ref>{{Cite journal| issn = 0022-1767| volume = 175| issue = 3| pages = 1785–1794| last = Nadesalingam | first = Jeya|author2=Alister W Dodds |author3=Kenneth B M Reid |author4=Nades Palaniyar | title = Mannose-binding lectin recognizes peptidoglycan via the N-acetyl glucosamine moiety, and inhibits ligand-induced proinflammatory effect and promotes chemokine production by macrophages| journal = Journal of Immunology | date = 2005-08-01 | doi=10.4049/jimmunol.175.3.1785| pmid = 16034120| doi-access = free}}</ref>
===Modulation of the adaptive immune system=== SP-A and SP-D can suppress activated T-lymphocytes and IL-2 (interleukin-2) production.<ref>{{Cite journal| issn = 0002-9513| volume = 275| issue = 4 Pt 1| pages = L679–686| last = Borron| first = P |author2=F X McCormack |author3=B M Elhalwagi |author4=Z C Chroneos |author5=J F Lewis |author6=S Zhu |author7=J R Wright |author8=V L Shepherd |author9=F Possmayer |author10=K Inchley |author11=L J Fraher| title = Surfactant protein A inhibits T cell proliferation via its collagen-like tail and a 210-kDa receptor| journal = The American Journal of Physiology| date = October 1998| doi = 10.1152/ajplung.1998.275.4.L679| pmid = 9755099}}</ref><ref>{{Cite journal| issn = 0022-1767| volume = 161| issue = 9| pages = 4599–4603| last = Borron| first = P J|author2=E C Crouch |author3=J F Lewis |author4=J R Wright |author5=F Possmayer |author6=L J Fraher | title = Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production| journal = Journal of Immunology | date = 1998-11-01| doi = 10.4049/jimmunol.161.9.4599| pmid = 9794387| s2cid = 26563431| doi-access = free}}</ref> SP-D increases bacterial antigen presentation by dendritic cells <ref>{{Cite journal| issn = 1040-0605| volume = 281| issue = 6| pages = L1453–1463| last = Brinker| first = K G|author2=E Martin |author3=P Borron |author4=E Mostaghel |author5=C Doyle |author6=C V Harding |author7=J R Wright | title = Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells| journal = American Journal of Physiology. Lung Cellular and Molecular Physiology|date=December 2001| doi = 10.1152/ajplung.2001.281.6.l1453 | pmid = 11704542| s2cid = 1356964}}</ref> whereas SP-A blocs differentation of the immature dendritic cells.<ref>{{Cite journal| doi = 10.1152/ajplung.00187.2002| pmid = 12388334| issn = 1040-0605| volume = 284| issue = 1| pages = L232–241| last = Brinker| first = Karen G|author2=Hollie Garner |author3=Jo Rae Wright | title = Surfactant protein A modulates the differentiation of murine bone marrow-derived dendritic cells| journal = American Journal of Physiology. Lung Cellular and Molecular Physiology| date = January 2003}}</ref>
===Modulation of allergic response=== Collectins SP-A and SP-D have anti-allergic effects: they inhibit IgE binding to allergens, decrease histamine release from basophils, and inhibit T-lymphocyte production in the late phase of the inflammation.<ref>{{Cite journal| issn = 0009-9104| volume = 130| issue = 1| pages = 19–24| last = Strong| first = P|author2=K B M Reid |author3=H Clark | title = Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus| journal = Clinical and Experimental Immunology|date=October 2002| doi=10.1046/j.1365-2249.2002.01968.x| pmid = 12296848| pmc=1906502}}</ref><ref>{{Cite journal| issn = 0009-9104| volume = 106| issue = 2| pages = 367–373| last = Wang| first = J Y|author2=U Kishore |author3=B L Lim |author4=P Strong |author5=K B Reid | title = Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens| journal = Clinical and Experimental Immunology| date = November 1996 | doi=10.1046/j.1365-2249.1996.d01-838.x| pmid = 8918587|pmc=2200585}}</ref><ref>{{Cite journal| issn = 1073-449X| volume = 158| issue = 2| pages = 510–518| last = Wang| first = J Y|author2=C C Shieh |author3=P F You |author4=H Y Lei |author5=K B Reid | title = Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma| journal = American Journal of Respiratory and Critical Care Medicine| date = August 1998 | doi=10.1164/ajrccm.158.2.9709111 | pmid=9700129}}</ref>
===Apoptosis=== Collectins SP-A and SP-D enhance clearance of apoptotic cells by macrophages.<ref>{{Cite journal| issn = 0022-1767| volume = 169| issue = 7| pages = 3978–3986| last = Vandivier| first = R William|author2=Carol Anne Ogden |author3=Valerie A Fadok |author4=Peter R Hoffmann |author5=Kevin K Brown |author6=Marina Botto |author7=Mark J Walport |author8=James H Fisher |author9=Peter M Henson |author10=Kelly E Greene | title = Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex| journal = Journal of Immunology| date = 2002-10-01 | doi=10.4049/jimmunol.169.7.3978| pmid = 12244199| doi-access=free }}</ref><ref>{{Cite journal| issn = 0022-1767| volume = 166| issue = 4| pages = 2727–2733| last = Schagat| first = T L |author2=J A Wofford |author3=J R Wright | title = Surfactant protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils| journal = Journal of Immunology | date = 2001-02-15| doi=10.4049/jimmunol.166.4.2727| pmid = 11160338| doi-access = free}}</ref>
===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.<ref>{{Cite journal| doi = 10.1078/0171-2985-00146| pmid = 12396007| issn = 0171-2985| volume = 205| issue = 4–5| pages = 455–466| last = Schwaeble| first = Wilhelm|author2=Mads R Dahl |author3=Steffen Thiel |author4=Cordula Stover |author5=Jens C Jensenius | title = The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes| journal = Immunobiology| date = September 2002}}</ref><ref>{{Cite journal| doi = 10.1038/nri800| pmid = 12033740| issn = 1474-1733| volume = 2| issue = 5| pages = 346–353| last = Fujita| first = Teizo| title = Evolution of the lectin-complement pathway and its role in innate immunity| journal = Nature Reviews. Immunology| date = May 2002| s2cid = 24314003}}</ref> 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.<ref>{{Cite journal| doi = 10.1078/0171-2985-00146| pmid = 12396007| issn = 0171-2985| volume = 205| issue = 4–5| pages = 455–466| last = Schwaeble| first = Wilhelm|author2=Mads R Dahl |author3=Steffen Thiel |author4=Cordula Stover |author5=Jens C Jensenius | title = The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes| journal = Immunobiology| date = September 2002}}</ref><ref>{{Cite journal| doi = 10.1038/386506a0| issn = 0028-0836| volume = 386| issue = 6624| pages = 506–510| last = Thiel| first = S |author2=T Vorup-Jensen |author3=C M Stover |author4=W Schwaeble |author5=S B Laursen |author6=K Poulsen |author7=A C Willis |author8=P Eggleton |author9=S Hansen |author10=U Holmskov |author11=K B Reid |author12=J C Jensenius | title = A second serine protease associated with mannan-binding lectin that activates complement| journal = Nature| date = 1997-04-03| pmid=9087411| bibcode = 1997Natur.386..506T| s2cid = 4261967}}</ref><ref>{{Cite journal| doi = 10.1073/pnas.1101748108| issn = 1091-6490| volume = 108| issue = 18| pages = 7523–7528| last = Schwaeble| first = Wilhelm J |author2=Nicholas J Lynch |author3=James E Clark |author4=Michael Marber |author5=Nilesh J Samani |author6=Youssif Mohammed Ali |author7=Thomas Dudler |author8=Brian Parent |author9=Karl Lhotta |author10=Russell Wallis |author11=Conrad A Farrar |author12=Steven Sacks |author13=Haekyung Lee |author14=Ming Zhang |author15=Daisuke Iwaki |author16=Minoru Takahashi |author17=Teizo Fujita |author18=Clark E Tedford |author19=Cordula M Stover | title = Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury| journal = Proceedings of the National Academy of Sciences of the United States of America| date = 2011-05-03 | pmid=21502512 | pmc=3088599| bibcode = 2011PNAS..108.7523S| doi-access = free}}</ref>
==Reviews== For more information and details see reviews:<ref>{{Cite journal| doi = 10.1111/j.1432-1033.2004.04040.x| pmid = 15030473| issn = 0014-2956| volume = 271| issue = 7| pages = 1229–1249| last = van de Wetering| first = J Koenraad |author2=Lambert M G van Golde |author3=Joseph J Batenburg | title = Collectins: players of the innate immune system| journal = European Journal of Biochemistry| date = April 2004| doi-access = free}}</ref><ref>{{Cite journal| doi = 10.1002/bies.20573| issn = 0265-9247| volume = 29| issue = 5 | pages = 452–464| last = Gupta| first = Garima|author2=Avadhesha Surolia| title = Collectins: sentinels of innate immunity| journal = BioEssays| date = May 2007| pmid=17450595| s2cid = 38069549}}</ref><ref>{{Cite journal| doi = 10.3389/fimmu.2012.00131| pmid = 22701116| pmc = 3369187| issn = 1664-3224| volume = 3| pages = 131| last = Nayak| first = Annapurna |author2=Eswari Dodagatta-Marri |author3=Anthony George Tsolaki |author4=Uday Kishore | title = An Insight into the Diverse Roles of Surfactant Proteins, SP-A and SP-D in Innate and Adaptive Immunity| journal = Frontiers in Immunology| year = 2012| doi-access = free}}</ref>
==References== {{reflist}} {{Lectins}} {{Pattern recognition receptors}}
Category:Lectins