Apoptosis

pp 1–11

Surfactant protein D delays Fas- and TRAIL-mediated extrinsic pathway of apoptosis in T cells

  • Pascal Djiadeu
  • Lakshmi P. Kotra
  • Neil Sweezey
  • Nades Palaniyar
Article

DOI: 10.1007/s10495-017-1348-4

Cite this article as:
Djiadeu, P., Kotra, L.P., Sweezey, N. et al. Apoptosis (2017). doi:10.1007/s10495-017-1348-4

Abstract

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.

Keywords

Surfactant protein DCollectinsMucosal surfaceFas:Fas LigandExtrinsic pathway of apoptosis

Abbreviations

BAL

Bronchoalveolar lavage

BSA

Bovine serum albumin

CD-3, CD-28

Cluster of differentiation 3 and 28

COPD

Chronic obstructive pulmonary disease

CRD

Carbohydrate recognition domain

DAPI

4′, 6-diamidino-2-phenylindole

DR

Death receptor

DIC

Differential interference contrast

EDTA

Ethylenediaminetetraacetic acid

FADD

Fas-associated death domain

FasL

Fas (CD95) Ligand

IL-2, IL-7

Interleukin 2 and 7

MFI

Median fluorescence intensity

PBMC

Peripheral blood mononuclear cells

PS

Phosphatidylserine

SLE

Systemic lupus erythematosus

SP-D

Surfactant protein D

TNFR1

Tumor necrosis factor receptor 1

TNFα

Tumor necrosis factor alpha

TRADD

Tumor necrosis factor receptor type-1 associated death domain

TRAIL

TNFα receptor apoptosis inducing ligand

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Pascal Djiadeu
    • 1
    • 2
  • Lakshmi P. Kotra
    • 2
    • 3
  • Neil Sweezey
    • 1
  • Nades Palaniyar
    • 1
    • 4
    • 5
  1. 1.Lung Innate Immunity Research Laboratory, Program in Physiology and Experimental MedicinePeter Gilgan Centre for Research and Learning, The Hospital for Sick ChildrenTorontoCanada
  2. 2.Department of Pharmaceutical Sciences, Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoCanada
  3. 3.Center for Molecular Design and Preformulations, Toronto General Research InstituteUniversity Health NetworkTorontoCanada
  4. 4.Departments of Laboratory Medicine and Pathobiology and Institute of Medical Sciences, Faculty of MedicineUniversity of TorontoTorontoCanada
  5. 5.Innate Immunity Research LaboratoryPeter Gilgan Centre for Research and Learning, The Hospital for Sick ChildrenTorontoCanada