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Innate immune collectin surfactant protein D enhances the clearance of DNA by macrophages and minimizes anti-DNA antibody generation

Innate immune collectin surfactant protein D enhances the clearance of DNA by macrophages and minimizes anti-DNA antibody generation
Innate immune collectin surfactant protein D enhances the clearance of DNA by macrophages and minimizes anti-DNA antibody generation
Dying microbes and necrotic cells release highly viscous DNA that induces inflammation and septic shock, and apoptotic cells display DNA, a potential autoantigen, on their surfaces. However, innate immune proteins that mediate the clearance of free DNA and surface DNA-containing cells are not clearly established. Pulmonary surfactant proteins (SP-) A and D are innate immune pattern recognition collectins that contain fibrillar collagen-like regions and globular carbohydrate recognition domains (CRDs). We have recently shown that collectins SP-A, SP-D, and mannose binding lectin recognize DNA and RNA via their collagen-like regions and CRDs. Here we show that SP-D enhances the uptake of Cy3-labeled fragments of DNA and DNA-coated beads by U937 human monocytic cells, in vitro. Analysis of DNA uptake by freshly isolated mouse alveolar macrophages shows that SP-D, but not SP-A, deficiency results in reduced clearance of DNA, ex vivo. Analysis of bronchoalveolar lavage fluid shows that SP-D- but not SP-A-deficient mice are defective in clearing free DNA from the lung. Additionally, both SP-A- and SP-D-deficient mice accumulate anti-DNA Abs in sera in an age-dependent manner. Thus, we conclude that collectins such as SP-A and SP-D reduce the generation of anti-DNA autoantibody, which may be explained in part by the defective clearance of DNA from the lungs in the absence of these proteins. Our findings establish two new roles for these innate immune proteins and that SP-D enhances efficient pinocytosis and phagocytosis of DNA by macrophages and minimizes anti-DNA Ab generation.
0022-1767
7352-7358
Palaniyar, Nades
262890ae-b2b1-4f9b-8129-08f8bcd6a399
Clark, Howard
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Nadesalingam, Jeya
5530d9f4-bb87-40ce-a3b1-34352d245a47
Shih, Michael J.
ba1ddd70-1ade-4dd7-b411-e44f84c51e77
Hawgood, Samuel
5e406d87-8445-448a-a068-b693d061d6dd
Reid, Kenneth B. M.
67b83320-96f6-41d0-ab1d-99430f39f904
Palaniyar, Nades
262890ae-b2b1-4f9b-8129-08f8bcd6a399
Clark, Howard
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Nadesalingam, Jeya
5530d9f4-bb87-40ce-a3b1-34352d245a47
Shih, Michael J.
ba1ddd70-1ade-4dd7-b411-e44f84c51e77
Hawgood, Samuel
5e406d87-8445-448a-a068-b693d061d6dd
Reid, Kenneth B. M.
67b83320-96f6-41d0-ab1d-99430f39f904

Palaniyar, Nades, Clark, Howard, Nadesalingam, Jeya, Shih, Michael J., Hawgood, Samuel and Reid, Kenneth B. M. (2005) Innate immune collectin surfactant protein D enhances the clearance of DNA by macrophages and minimizes anti-DNA antibody generation. Journal of Immunology, 174 (11), 7352-7358.

Record type: Article

Abstract

Dying microbes and necrotic cells release highly viscous DNA that induces inflammation and septic shock, and apoptotic cells display DNA, a potential autoantigen, on their surfaces. However, innate immune proteins that mediate the clearance of free DNA and surface DNA-containing cells are not clearly established. Pulmonary surfactant proteins (SP-) A and D are innate immune pattern recognition collectins that contain fibrillar collagen-like regions and globular carbohydrate recognition domains (CRDs). We have recently shown that collectins SP-A, SP-D, and mannose binding lectin recognize DNA and RNA via their collagen-like regions and CRDs. Here we show that SP-D enhances the uptake of Cy3-labeled fragments of DNA and DNA-coated beads by U937 human monocytic cells, in vitro. Analysis of DNA uptake by freshly isolated mouse alveolar macrophages shows that SP-D, but not SP-A, deficiency results in reduced clearance of DNA, ex vivo. Analysis of bronchoalveolar lavage fluid shows that SP-D- but not SP-A-deficient mice are defective in clearing free DNA from the lung. Additionally, both SP-A- and SP-D-deficient mice accumulate anti-DNA Abs in sera in an age-dependent manner. Thus, we conclude that collectins such as SP-A and SP-D reduce the generation of anti-DNA autoantibody, which may be explained in part by the defective clearance of DNA from the lungs in the absence of these proteins. Our findings establish two new roles for these innate immune proteins and that SP-D enhances efficient pinocytosis and phagocytosis of DNA by macrophages and minimizes anti-DNA Ab generation.

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Published date: 1 June 2005

Identifiers

Local EPrints ID: 44258
URI: http://eprints.soton.ac.uk/id/eprint/44258
ISSN: 0022-1767
PURE UUID: 8f78a91a-67ca-446c-85e4-59b0a5e6e19b

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Date deposited: 21 Feb 2007
Last modified: 15 Mar 2024 09:02

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Contributors

Author: Nades Palaniyar
Author: Howard Clark
Author: Jeya Nadesalingam
Author: Michael J. Shih
Author: Samuel Hawgood
Author: Kenneth B. M. Reid

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