| The collectins - C-type lectins containing collagen-like regions - assessment of their roles in innate immunity | ||||||||
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Professor Kenneth
B M Reid BSc PhD FRS |
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Last checked:
10.01.2007
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The Collectin family is composed of three serum proteins - mannan binding lectin (MBL), bovine conglutinin (BK) and collectin-43 (CL-43) - and two lung surfactant proteins (SP-A and SP-D). An important structural feature of these proteins is that their C-type lectin carbohydrate binding domains (CRDs) are clustered as trimers, in each subunit, via an alpha-helical coiled-coil located at the C-terminal end of a collagen-like triple-helix. Disulphide bonding between subunits yields higher oligomers. This arrangement of CRDs allows the collectins to bind tightly to arrays of carbohydrates, of the type found on the surfaces of viral, bacterial and fungal pathogens, thus agglutinating these microorganisms and triggering the host’s killing and clearance defence mechanisms. One of the collectins, serum MBL brings about activation of the complement system and thus can recruit all the inflammatory and lytic properties associated with that system. The other collectins do not activate complement but are very effective at agglutination of pathogens and in the triggering of phagocytic cells such as macrophages and neutrophils. The research on the lung surfactant proteins SP-A and SP-D is concerned primarily with the roles they may play in: modulating allergic reactions, by binding to glycosylated allergens and thus blocking the binding of IgE to these allergens; protection against certain lung infections with organisms such as Pseudomonas aeruginosa, Candida albicans, and Aspergillus fumigatus, with a view to developing therapeutic strategies. SP-A and SP-D are also found in the gastrointestinal tract, tear ducts, synovial fluid which is suggestive that they may be important in combating infection at sites other than the lung. Much of the research is centred around the protein engineering of recombinant fragments of SP-A and SP-D, using yeast, E. coli or mammalian expression systems. The expressed material is being used for functional studies, (binding to pathogens, triggering of phagocytic cells, identification of cell-surface receptors) and also structural studies (NMR, crystallography, in collaboration with other groups within the Biochemistry Department). |
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Key publications Eggleton, P. and Reid, K.B.M. (1999) Lung surfactant proteins involved in innate immunity.Curr. Opin. Immunol. 11, 28-33. Clark, H., Palaniyar, N., Strong, P., Edmondson, J., Hawgood, S. and Reid, K.B.M.(2002) Surfactant protein reduces alveolar macrophage apoptosis in vivo. J. Immunol. 169, 2892-2899. Madan, T., Kishore, U., Singh, M., Strong, P., Clark, H., Hussain, E.M., Reid, K.B.M. and Sarma, P.U.Lung surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J. Clin. Invest.(2001) 107, 467-475. Madan, T., Kishore, U., Singh, M., Strong, P., Hussain, E.M., Reid, K.B.M. and Sarma, P.U. (2001) Protective role of lung surfactant D in a murine model of invasive pulmonary aspergillosis. Infection and Immunity 69, 2728-2731. Lawson, P.R.
and Reid, K.B.M. (2000) Håkansson, K. and Reid, K.B.M. (2000) Collectin structure: A review. Protein Science 9, 1607-1617.
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