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Surface-bound myeloperoxidase is a ligand for recognition of late apoptotic neutrophils by human lung surfactant proteins A and D

Record type: Article

Surfactant proteins A (SP-A) and D (SP-D), both members of the collectin family, play a well established role in apoptotic cell recognition and clearance. Recent in vitro data show that SP-A and SP-D interact with apoptotic neutrophils in a distinct manner. SP-A and SP-D bind in a Ca2+-dependent manner to viable and early apoptotic neutrophils whereas the much greater interaction with late apoptotic neutrophils is Ca2+-independent. Cell surface molecules on the apoptotic target cells responsible for these interactions had not been identified and this study was done to find candidate target molecules. Myeloperoxidase (MPO), a specific intracellular defense molecule of neutrophils that becomes exposed on the outside of the cell upon apoptosis, was identified by affinity purification, mass-spectrometry and western blotting as a novel binding molecule for SP-A and SP-D. To confirm its role in recognition, it was shown that purified immobilised MPO binds SP-A and SP-D, and that MPO is surface-exposed on late apoptotic neutrophils. SP-A and SP-D inhibit binding of an anti-MPO monoclonal Ab to late apoptotic cells. Fluorescence microscopy confirmed that anti-MPO mAb and SP-A/SP-D colocalise on late apoptotic neutrophils. Desmoplakin was identified as a further potential ligand for SP-A, and neutrophil defensin as a target for both proteins.

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Citation

Jakel, Anne, Clark, Howard, Reid, Kenneth and Sim, Robert B. (2010) Surface-bound myeloperoxidase is a ligand for recognition of late apoptotic neutrophils by human lung surfactant proteins A and D Protein & Cell, 1, (6), pp. 563-572. (doi:10.1007/s13238-010-0076-0). (PMID:21204009).

More information

Published date: June 2010
Keywords: sp-a, sp-d, myeloperoxidase, neutrophils, flow cytometry, mass spectrometry

Identifiers

Local EPrints ID: 176007
URI: http://eprints.soton.ac.uk/id/eprint/176007
ISSN: 1674-800X
PURE UUID: c2b04a64-1e37-457f-bccd-802a0c166570

Catalogue record

Date deposited: 02 Mar 2011 11:20
Last modified: 18 Jul 2017 12:08

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Contributors

Author: Anne Jakel
Author: Howard Clark
Author: Kenneth Reid
Author: Robert B. Sim

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