CoChat
Sign Up
Cited by 36Cell death mechanisms and regulationBlood transfusion and managementNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion

Open access
Fan, Yuping, Teng, Yan, Loison, Fabien, Pang, Aiming, Kasorn, Anongnard, Shao, Xinqi, Zhang, Cunling, Ren, Qian +12 more·2021·Science Translational Medicine
DOI 10.1126/scitranslmed.abb1069PMC PMC10336857
Open this paper in CoChat — free accountOpen PDF

Abstract

Survival of neutrophils is prolonged, and their function is preserved by simultaneously targeting multiple cell death pathways.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1126/scitranslmed.abb1069

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Neutrophils have a short life span and undergo apoptosis within a few hours.

    “Since neutrophils have a short life span and undergo apoptosis within a few hours”

    From Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors (2025) · cites this paper as [82]

    The Discussion describes neutrophils as short-lived, and the Introduction identifies apoptosis as one of their death pathways. But the Results report an untreated half-life of less than 24 hours in culture, not that neutrophils undergo apoptosis within a few hours; they also distinguish apoptotic from lytic death. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The pan-caspase inhibitor Q-VD-Oph inhibits spontaneous neutrophil apoptosis and consequently increases neutrophil lifespan.

    “the cultivation of neutrophils in the polarization experiments was carried out in the presence of 3 mM pan-caspase inhibitor Q-VD-Oph (Selleckchem, cat. no. S7311) to inhibit spontaneous neutrophil apoptosis and, consequently, increase their lifespan82.”

    From Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors (2025) · cites this paper as [82]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 40

  1. [1]White L, Ybarra M, Neutropenic fever. Hematol. Oncol. Clin. North Am 31, 981– 993 (2017). 29078933
  2. [2]Wingard JR, Eldjerou L, Leather H, Use of antibacterial prophylaxis in patients with chemotherapy-induced neutropenia. Curr. Opin. Hematol. 19, 21– 26 (2012). 22080847
  3. [3]Bennett CL, Djulbegovic B, Norris LB, Armitage JO, Colony-stimulating factors for febrile neutropenia during cancer therapy. N. Engl. J. Med. 368, 1131– 1139 (2013). 23514290 PMC3947590
  4. [4]Anderlini P, Przepiorka D, Champlin R, Korbling M, Biologic and clinical effects of granulocyte colony-stimulating factor in normal individuals. Blood 88, 2819– 2825 (1996). 8874177
  5. [5]Dale DC, Price TH, Granulocyte transfusion therapy: A new era? Curr. Opin. Hematol. 16, 1– 2 (2009). 19057197 PMC2674763
  6. [6]Goldfinger D, Lu Q, in UpToDate AJ Rosmarin Silvergleid, A. G., Eds. (Wolters Kluwer, 2020), vol. 2020.
  7. [7]Netelenbos T, Massey E, de Wreede LC, Harding K, Hamblin A, Sekhar M, Li A, Ypma PF, Ball L, Zwaginga JJ, Stanworth SJ, The burden of invasive infections in neutropenic patients: Incidence, outcomes, and use of granulocyte transfusions. Transfusion 59, 160– 168 (2019). 30383912 PMC7379528
  8. [8]Price TH, Boeckh M, Harrison RW, McCullough J, Ness PM, Strauss RG, Nichols WG, Hamza TH, Cushing MM, King KE, Young J-AH, Williams E, McFarland J, Holter Chakrabarty J, Sloan SR, Friedman D, Parekh S, Sachais BS, Kiss JE, Assmann SF, Efficacy of transfusion with granulocytes from G-CSF/ dexamethasone-treated donors in neutropenic patients with infection. Blood 126, 2153– 2161 (2015). 26333778 PMC4626256
  9. [9]Teng Y, Luo HR, Kambara H, Heterogeneity of neutrophil spontaneous death. Am. J. Hematol. 92, E156– E159 (2017). 28437875 PMC5657301
  10. [10]Zhu D, Hattori H, Jo H, Jia Y, Subramanian KK, Loison F, You J, Le Y, Honczarenko M, Silberstein L, Luo HR, Deactivation of phosphatidylinositol 3,4,5-trisphosphate/Akt signaling mediates neutrophil spontaneous death. Proc. Natl. Acad. Sci. U.S.A. 103, 14836– 14841 (2006). 16988010 PMC1595438
  11. [11]Xu Y, Loison F, Luo HR, Neutrophil spontaneous death is mediated by down-regulation of autocrine signaling through GPCR, PI3Kγ, ROS, and actin. Proc. Natl. Acad. Sci. U.S.A. 107, 2950– 2955 (2010). 20133633 PMC2840335
  12. [13]Kambara H, Liu F, Zhang X, Liu P, Bajrami B, Teng Y, Zhao L, Zhou S, Yu H, Zhou W, Silberstein LE, Cheng T, Han M, Xu Y, Luo HR, Gasdermin D exerts anti-inflammatory effects by promoting neutrophil death. Cell Rep. 22, 2924– 2936 (2018). 29539421 PMC5878047
  13. [14]Wang X, He Z, Liu H, Yousefi S, Simon H-U, Neutrophil necroptosis is triggered by ligation of adhesion molecules following GM-CSF priming. 197, 4090– 4100 (2016). 27815445
  14. [15]Luo HR, Loison F, Constitutive neutrophil apoptosis: Mechanisms and regulation. Am. J. Hematol. 83, 288– 295 (2008). 17924549
  15. [16]Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y, Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc. Natl. Acad. Sci. U.S.A. 101, 7618– 7623 (2004). 15128949 PMC419655
  16. [17]Li Y, Jia Y, Pichavant M, Loison F, Sarraj B, Kasorn A, You J, Robson BE, Umetsu DT, Mizgerd JP, Ye K, Luo HR, Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia. Blood 113, 4930– 4941 (2009). 19286998 PMC2686143
  17. [18]Prasad A, Jia Y, Chakraborty A, Li Y, Jain SK, Zhong J, Roy SG, Loison F, Mondal S, Sakai J, Blanchard C, Snyder SH, Luo HR, Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)trisphosphate signaling. Nat. Immunol. 12, 752– 760 (2011). 21685907 PMC3140608
  18. [19]Sakai J, Li J, Subramanian KK, Mondal S, Bajrami B, Hattori H, Jia Y, Dickinson BC, Zhong J, Ye K, Chang CJ, Ho YS, Zhou J, Luo HR, Reactive oxygen species-induced actin glutathionylation controls actin dynamics in neutrophils. Immunity 37, 1037– 1049 (2012). 23159440 PMC3525814
  19. [20]Li Y, Prasad A, Jia Y, Roy SG, Loison F, Mondal S, Kocjan P, Silberstein LE, Ding S, Luo HR, Pretreatment with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor SF1670 augments the efficacy of granulocyte transfusion in a clinically relevant mouse model. Blood 117, 6702– 6713 (2011). 21521784 PMC3123029
  20. [21]Jia Y, Subramanian KK, Erneux C, Pouillon V, Hattori H, Jo H, You J, Zhu D, Schurmans S, Luo HR, Inositol 1,3,4,5-tetrakisphosphate negatively regulates phosphatidylinositol-3,4,5-trisphosphate signaling in neutrophils. Immunity 27, 453– 467 (2007). 17825589 PMC2084373
  21. [22]Duffin R, Leitch AE, Fox S, Haslett C, Rossi AG, Targeting granulocyte apoptosis: Mechanisms, models, and therapies. Immunol. Rev. 236, 28– 40 (2010). 20636806
  22. [23]Nesher L, Rolston KVI, The current spectrum of infection in cancer patients with chemotherapy related neutropenia. Infection 42, 5– 13 (2014). 23975584
  23. [24]Trump LR, Nayak RC, Singh AK, Emberesh S, Wellendorf AM, Lutzko CM, Cancelas JA, Neutrophils derived from genetically modified human induced pluripotent stem cells circulate and phagocytose bacteria in vivo. Stem Cells Transl. Med. 8, 557– 567 (2019). 30793529 PMC6525559
  24. [25]Monceaux V, Chiche-Lapierre C, Chaput C, Witko-Sarsat V, Prevost MC, Taylor CT, Ungeheuer M-N, Sansonetti PJ, Marteyn BS, Anoxia and glucose supplementation preserve neutrophil viability and function. Blood 128, 993– 1002 (2016). 27402974
  25. [26]Marfin AA, Price TH, Granulocyte transfusion therapy. J. Intensive Care Med. 30, 79– 88 (2015). 23920161
  26. [27]Lane TA, Granulocyte storage. Transfus. Med. Rev. 4, 23– 34 (1990). 2134614
  27. [28]Pric THe, Dale DC, Blood kinetics and in vivo chemotaxis of transfused neutrophils: Effect of colllection method, donor corticosteroid treatment, and short-term storage. Blood 54, 977 –986 (1979). 497403
  28. [29]Glasser L, Lane TA, McCullough J, Price TH, Panel VII: Neutrophil concentrates: Functional considerations, storage, and quality control. J. Clin. Apher. 1, 179– 184 (1983). 6085931
  29. [30]Drewniak A, Boelens J-J, Vrielink H, Tool ATJ, Bruin MCA, van den Heuvel-Eibrink M, Ball L, van de Wetering MD, Roos D, Kuijpers TW, Granulocyte concentrates: Prolonged functional capacity during storage in the presence of phenotypic changes. Haematologica 93, 1058– 1067 (2008). 18508794
  30. [32]Caspar CB, Seger RA, Burger J, Gmur J, Effective stimulation of donors for granulocyte transfusions with recombinant methionyl granulocyte colony-stimulating factor. Blood 81, 2866– 2871 (1993). 7684619
  31. [33]Bensinger WI, Price TH, Dale DC, Appelbaum FR, Clift R, Lilleby K, Williams B, Storb R, Thomas ED, Buckner CD, The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis. Blood 81, 1883– 1888 (1993). 7681705
  32. [34]Colotta F, Re F, Polentarutti N, Sozzani S, Mantovani A, Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood 80, 2012– 2020 (1992). 1382715
  33. [35]Leavey PJ, Thurman G, Ambruso DR, Functional characteristics of neutrophils collected and stored after administration of G-CSF. Transfusion 40, 414– 419 (2000). 10773052
  34. [36]Hubel K, Rodger E, Gaviria JM, Price TH, Dale DC, Liles WC, Effective storage of granulocytes collected by centrifugation leukapheresis from donors stimulated with granulocyte-colony-stimulating factor. Transfusion 45, 1876– 1889 (2005). 16371040
  35. [37]van Raam BJ, Drewniak A, Groenewold V, van den Berg TK, Kuijpers TW, Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3. Blood 112, 2046– 2054 (2008). 18524991 PMC2518906
  36. [38]Maianski NA, Mul FPJ, van Buul JD, Roos D, Kuijpers TW, Granulocyte colony-stimulating factor inhibits the mitochondria-dependent activation of caspase-3 in neutrophils. Blood 99, 672– 679 (2002). 11781253
  37. [39]Goldfinger D, Lu Q, in UpToDate, Post TW, Silvergleid AJ, Rosmarin AG. (Wolters Kluwer, 2020).
  38. [40]Dahlgren C, Karlsson A, Respiratory burst in human neutrophils. J. Immunol. Methods 232, 3– 14 (1999). 10618505
  39. [41]Subramanian KK, Jia Y, Zhu D, Simms BT, Jo H, Hattori H, You J, Mizgerd JP, Luo HR, Tumor suppressor PTEN is a physiologic suppressor of chemoattractant-mediated neutrophil functions. Blood 109, 4028– 4037 (2007). 17202315 PMC1874585
  40. [42]Su X, Johansen M, Looney MR, Brown EJ, Matthay MA, CD47 deficiency protects mice from lipopolysaccharide-induced acute lung injury and Escherichia coli pneumonia. J. Immunol 180, 6947– 6953 (2008). 18453616 PMC2771449

Cited by

Sorted by citations

Authors
Fan, Y., Teng, Y., Loison, F., Pang, A., Kasorn, A., Shao, X., Zhang, C., Ren, Q., Yu, H., Zheng, Y., Cancelas, J. A., Manis, J., Chai, L., Park, S.-Y., Zhao, L., Xu, Y., Feng, S., Silberstein, L. E., Ma, F., & Luo, H. R.
Affiliations
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Boston Children's Hospital (US)
  • Cincinnati Children's Hospital Medical Center (US)
  • VA Boston Healthcare System (US)
  • Experimental Hematology and Cancer Biology Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
Corresponding author
  • Fan, Yuping
  • Teng, Yan
  • Ma, Fengxia
  • Luo, Hongbo R.
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2021-07-28
Volume
13
Issue
604
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
DOI
10.1126/scitranslmed.abb1069
PMC
PMC10336857
OpenAlex
W3185305745
Cited by
36
References
2
Citations by year
2026: 9 · 2025: 13 · 2024: 6 · 2023: 3 · 2022: 5
FWCI
1.10
Type
journal article
Language
en
Open access
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (R01 AI142642, R01 AI145274, R01 AI141386, P01 HL095489, 1 R01 AI142642, 1 R01 AI145274, 1 R01 AI141386, R01HL092020)
  • Flight Attendant Medical Research Institute (NIH P01 HL095489, CIA 123008)
  • National Natural Sciences Foundation of China (81970107)
  • HRL (1 R01 AI142642, 1 R01 AI145274, 1 R01 AI141386, R01HL092020)
  • City University London (18JCYBJC25700)
  • Chinese Academy of Medical Sciences (2016-I2M-1-017, 2018RC31002, 2018PT32034)
  • Natural Science Foundation of Tianjin City (18JCYBJC25700)
  • National Natural Science Foundation of China (81970107, 31471116)
  • HRL This (NIH P01 HL095489)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Biochemistry › Blood transfusion and management
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
granulocyte transfusion, neutrophils, cell death pathways, caspase inhibition, lysosomal membrane permeabilization, granulocyte colony-stimulating factor, neutropenia, bacterial pneumonia, systemic candidiasis, phagocytosis, reactive oxygen species
MeSH terms
Aged, Animals, Humans, Neutropenia, Neutrophils, Granulocyte Colony-Stimulating Factor, Cell Death, Leukocyte Transfusion, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review