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

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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.

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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

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Acknowledgements

This study was funded by Canadian Institutes of Health Research (MOP-111012, N.P) and Cystic Fibrosis Canada (2619, N.P and 3029 to N.S and N.P).

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Authors and Affiliations

  1. 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

    Pascal Djiadeu, Neil Sweezey & Nades Palaniyar

  2. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada

    Pascal Djiadeu & Lakshmi P. Kotra

  3. Center for Molecular Design and Preformulations, Toronto General Research Institute, University Health Network, 101 College Street, Toronto, ON, M5G 1L7, Canada

    Lakshmi P. Kotra

  4. Departments of Laboratory Medicine and Pathobiology and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5G 1X8, Canada

    Nades Palaniyar

  5. 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

Authors
  1. Pascal Djiadeu
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  2. Lakshmi P. Kotra
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  3. Neil Sweezey
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  4. Nades Palaniyar
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Correspondence to Nades Palaniyar.

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Djiadeu, P., Kotra, L.P., Sweezey, N. et al. Surfactant protein D delays Fas- and TRAIL-mediated extrinsic pathway of apoptosis in T cells. Apoptosis 22, 730–740 (2017). https://doi.org/10.1007/s10495-017-1348-4

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  • DOI: https://doi.org/10.1007/s10495-017-1348-4

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