Surface-bound myeloperoxidase is a ligand for recognition of late apoptotic neutrophils by human lung surfactant proteins A and D.
10.1007/s13238-010-0076-0
- Author:
Anne JÄKEL
1
;
Howard CLARK
;
Kenneth B M REID
;
Robert B SIM
Author Information
1. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Binding, Competitive;
Fluorescent Antibody Technique, Indirect;
Humans;
Neutrophils;
chemistry;
cytology;
metabolism;
Peroxidase;
isolation & purification;
metabolism;
Protein Binding;
Pulmonary Surfactant-Associated Protein A;
isolation & purification;
metabolism;
Pulmonary Surfactant-Associated Protein D;
isolation & purification;
metabolism
- From:
Protein & Cell
2010;1(6):563-572
- CountryChina
- Language:English
-
Abstract:
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 Ca(2+)-dependent manner to viable and early apoptotic neutrophils whereas the much greater interaction with late apoptotic neutrophils is Ca(2+)-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.
