title: Surfactant protein A (SP-A) binds to phosphatidylserine and competes with annexin V binding on late apoptotic cells.
abstract: The role of surfactant protein A (SP-A) in the recognition and clearance of apoptotic cells is well established, but to date, it is still not clear which surface molecules of apoptotic cells are involved in the process. Here we present evidence that phosphatidylserine (PS) is a relevant binding molecule for human SP-A. The binding is Ca(2+)-dependent and is not inhibited by mannose, suggesting that the sugar-binding site of the carbohydrate recognition domain (CRD) of SP-A is not involved. Flow cytometry studies on apoptotic Jurkat cells revealed apparent inhibition of annexin V binding by increasing concentrations of SP-A in late apoptotic but not early apoptotic cells, and this was consistent for Jurkat cells and neutrophils. Supporting these data, confocal microscopy results show a co-localisation of annexin V and SP-A in late apoptotic but not early apoptotic cells. However, we cannot conclude that this inhibition is exclusively due to the binding of SP-A to PS on the cell surface, as annexin V is not wholly specific for PS and SP-A also interacts with other phospholipids that might become exposed on the apoptotic cell surface.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. anne.jakel@mansfield.oxon.org
authors.forename: Anne
authors.initials: A
authors.lastname: Jäkel
authors.forename: Kenneth B M
authors.initials: KB
authors.lastname: Reid
authors.forename: Howard
authors.initials: H
authors.lastname: Clark
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D002262:Carboxy-Lyases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000502:physiology; D010718:Phosphatidylserines / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D010718:Phosphatidylserines; D037662:Pulmonary Surfactant-Associated Protein A; D002262:Carboxy-Lyases; C022353:phosphatidylserine decarboxylase