Surface-bound myeloperoxidase is a ligand for recognition of late apoptotic neutrophils by human lung surfactant proteins A and D
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), 563-572. (doi:10.1007/s13238-010-0076-0). (PMID:21204009).
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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.
|Keywords:||sp-a, sp-d, myeloperoxidase, neutrophils, flow cytometry, mass spectrometry|
|Subjects:||Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine
|Divisions:||University Structure - Pre August 2011 > School of Medicine
|Date Deposited:||02 Mar 2011 11:20|
|Last Modified:||25 Apr 2013 23:45|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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