Surfactant protein D delays Fas- and TRAIL-mediated extrinsic pathway of apoptosis in T cells.
Only a few extracellular soluble proteins are known to modulate apoptosis. We considered that surfactant-associated protein D (SP-D), an innate immune collectin present on many mucosal surfaces, could regulate apoptosis. Although SP-D is known to be important for immune cell homeostasis, whether SP-D affects apoptosis is unknown. In this study we aimed to determine the effects of SP-D on Jurkat T cells and human T cells dying by apoptosis. Here we show that SP-D binds to Jurkat T cells and delays the progression of Fas (CD95)-Fas ligand and TRAIL-TRAIL receptor induced, but not TNF-TNF receptor-mediated apoptosis. SP-D exerts its effects by reducing the activation of initiator caspase-8 and executioner caspase-3. SP-D also delays the surface exposure of phosphatidylserine. The effect of SP-D was ablated by the presence of caspase-8 inhibitor, but not by intrinsic pathway inhibitors. The binding ability of SP-D to dying cells decreases during the early stages of apoptosis, suggesting the release of apoptotic cell surface targets during apoptosis. SP-D also delays FasL-induced death of primary human T cells. SP-D delaying the progression of the extrinsic pathway of apoptosis could have important implications in regulating immune cell homeostasis at mucosal surfaces.
Lung Innate Immunity Research Laboratory, Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay St, Toronto, ON, M5G 0A4, Canada.|Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.
Pascal
P
Djiadeu
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.|Center for Molecular Design and Preformulations, Toronto General Research Institute, University Health Network, 101 College Street, Toronto, ON, M5G 1L7, Canada.
Lakshmi P
LP
Kotra
Lung Innate Immunity Research Laboratory, Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay St, Toronto, ON, M5G 0A4, Canada.
Neil
N
Sweezey
Lung Innate Immunity Research Laboratory, Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay St, Toronto, ON, M5G 0A4, Canada. nades.palaniyar@sickkids.ca.|Departments of Laboratory Medicine and Pathobiology and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5G 1X8, Canada. nades.palaniyar@sickkids.ca.|Innate Immunity Research Laboratory, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay St, Toronto, ON, M5G 0A4, Canada. nades.palaniyar@sickkids.ca.
Nades
N
Palaniyar
D017209:Apoptosis / Q000235:genetics* / Q000276:immunology; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics* / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D053222:Fas Ligand Protein; D037663:Pulmonary Surfactant-Associated Protein D; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C439524:TNF protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor
Collectins; Extrinsic pathway of apoptosis; Fas:Fas Ligand; Mucosal surface; Surfactant protein D