Chapter 10 : Collectins and the Acute-Phase Response

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This chapter focuses on one essential component of the innate immune system, that is, non-antibody-mediated pathogen recognition and opsonization. In particular, the focus is on the collectin subgroup of the superfamily of lectins, known as the C-type lectins. The collectins appear to play an important role as pattern recognition molecules in the protection of mammals from viral, fungal, and bacterial infection. In humans and rodents, mannose-binding lectin (MBL) is the only major serum collectin, although low levels of both surfactant protein A (SP-A) and surfactant protein D (SP-D) are also found in serum. Three additional serum collectins, con-glutinin, CL-43, and CL-46, have been identified in the cow but not yet in other species. The chapter describes the structure of the collectin. For MBL as a serum protein, its role appears to be as an ante-antibody as it acts like a broad-spectrum antibody and is able to activate complement via a novel mechanism. The chapter explores the experimental evidence that supports these contentions. The findings that SP-A and SP-D play a pivotal role in the regulation of macrophagemediated inflammation in the lung, in the defense against invasion by pathogens, and in modulating inflammatory responses to infection and allergenic stimuli have intriguing clinical implications for a range of lung diseases. A great deal of progress has been made in defining the role for collectins as first-line host defense molecules. The exciting possibility exists that this knowledge may be harnessed and translated into novel adjuvant therapies.

Citation: Clark H, Reid K, Stehle T, Ezekowitz A. 2004. Collectins and the Acute-Phase Response, p 199-218. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch10
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Image of FIGURE 1

Mammalian lectins. The collectins form a subgroup of the C-type lectin superfamily. The lung collectins SP-A and SP-D, with the serum collectin MBL, are the only secreted collectins so far described in humans.

Citation: Clark H, Reid K, Stehle T, Ezekowitz A. 2004. Collectins and the Acute-Phase Response, p 199-218. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch10
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Image of FIGURE 2

MBL, SP-A, and SP-D are collectins with collagenous and carbohydrate-binding domains. Oligomerization of the trimeric building blocks greatly enhances the avidity of binding to carbohydrate targets via the CRDs.

Citation: Clark H, Reid K, Stehle T, Ezekowitz A. 2004. Collectins and the Acute-Phase Response, p 199-218. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch10
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Image of FIGURE 3

Comparison of the structural features of the CRDs from MBL and SP-D. Both MBL and SP-D trimers are very similar in structure. A striking feature of the SP-D trimer structure is the central area containing positively charged residues (indicated in dark gray) that may facilitate its interaction with negatively charged residues on pathogen targets such as LPS.

Citation: Clark H, Reid K, Stehle T, Ezekowitz A. 2004. Collectins and the Acute-Phase Response, p 199-218. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch10
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Generic image for table

Microbial targets of SP-A

Citation: Clark H, Reid K, Stehle T, Ezekowitz A. 2004. Collectins and the Acute-Phase Response, p 199-218. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch10
Generic image for table

Microbial targets of SP-D

Citation: Clark H, Reid K, Stehle T, Ezekowitz A. 2004. Collectins and the Acute-Phase Response, p 199-218. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch10
Generic image for table

Microbial targets of MBL

Citation: Clark H, Reid K, Stehle T, Ezekowitz A. 2004. Collectins and the Acute-Phase Response, p 199-218. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch10

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