CoChat
Sign Up
Cited by 43Phagocytosis and Immune RegulationCellular transport and secretionCell death mechanisms and regulation

Inactivation of Rab11a GTPase in Macrophages Facilitates Phagocytosis of Apoptotic Neutrophils

Open access
Jiang, Chunling, Liu, Zheng, Hu, Rong, Bo, Lulong, Minshall, Richard D, Malik, Asrar B, Hu, Guochang·2017·The Journal of Immunology
DOI 10.4049/jimmunol.1601495PMC PMC5296368
Open this paper in CoChat — free account

Abstract

The timely and efficient clearance of apoptotic neutrophils by macrophages (efferocytosis) is required for the resolution of inflammation and tissue repair, but the regulatory mechanisms remain unclear. In this study, we investigated the role of the small GTPase Ras-related protein in brain (Rab)11a in regulating efferocytosis, and on this basis the resolution of inflammatory lung injury. We observed that apoptotic neutrophil feeding induced a rapid loss of Rab11a activity in bone marrow–derived macrophages and found that depletion of Rab11a in macrophages by small interfering RNA dramatically increased the phagocytosis of apoptotic neutrophils compared with control cells. Additionally, overexpression of wild-type Rab11a inhibited macrophage efferocytosis, whereas overexpression of dominant-negative Rab11a (Rab11a S25N) increased the clearance of apoptotic neutrophils. Rab11a knockdown also increased the surface level of CD36 in macrophages, but it reduced cell surface expression of a disintegrin and metalloproteinase (ADAM) 17. Depletion of ADAM17 rescued the decreased surface CD36 expression found in macrophages overexpressing wild-type Rab11a. Also, blockade of CD36 abolished the augmented efferocytosis seen in Rab11a-depleted macrophages. In mice challenged with endotoxin, intratracheal instillation of Rab11a-depleted macrophages reduced neutrophil count in bronchoalveolar lavage fluid, increased the number of macrophages containing apoptotic neutrophils, and prevented inflammatory lung injury. Thus, Rab11a inactivation in macrophages as a result of apoptotic cell binding initiates phagocytosis of apoptotic neutrophils via the modulation of ADAM17-mediated CD36 cell surface expression. Our results raise the possibility that inhibition of Rab11a activity in macrophages is a promising strategy for activating the resolution of inflammatory lung injury.

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 · 10.4049/jimmunol.1601495

Cites

3 of 3 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?

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: 42

  1. [1]Rock KL Lai JJ Kono H 2011 Innate and adaptive immune responses to cell death Immunol Rev 243 191 205 21884177 PMC3170128
  2. [2]Ortega-Gomez A Perretti M Soehnlein O 2013 Resolution of inflammation: an integrated view EMBO Mol Med 5 661 674 23592557 PMC3662311
  3. [3]Korns D Frasch SC Fernandez-Boyanapalli R Henson PM Bratton DL 2011 Modulation of macrophage efferocytosis in inflammation Front Immunol 2 57 22566847 PMC3342042
  4. [4]Voll RE Herrmann M Roth EA Stach C Kalden JR 1997 Immunosuppressive effect of apoptotic cells Nature 390 350 351 9389474
  5. [5]Fadok VA Bratton DL Rose DM Pearson A Ezekewitz RA Henson PM 2000 A receptor for phosphatidyiserine-specific clearance of apoptotic cells Nature 405 85 90 10811223
  6. [6]Basil MC Levy BD 2016 Specialized pro-resolving mediators: endogenous regulators of infection and inflammation Nat Rev Immunol 16 51 67 26688348 PMC5242505
  7. [7]Headland SE Norling LV 2015 The resolution of inflammation: Principles and challenges Semin Immunol 27 149 160 25911383
  8. [8]Ravichandran KS Lorenz U 2007 Engulfment of apoptotic cells: signals for a good meal Nat Rev Immunol 7 964 974 18037898
  9. [11]Hochreiter-Hufford A Ravichandran KS 2013 Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion Cold Spring Harb Perspect Biol 5 a008748 23284042 PMC3579390
  10. [12]Schwartz SL Cao C Pylypenko O Rak A Wandinger-Ness A 2007 Rab GTPases at a glance J Cell Sci 120 3905 3910 17989088
  11. [13]Stenmark H 2009 Rab GTPases as coordinators of vesicle traffic Nat Rev Mol Cell Biol 10 513 525 19603039
  12. [14]Bhuin T Roy JK 2015 Rab11 in disease progression Int J Mol Cell Med 4 1 8 25815277 PMC4359700
  13. [15]Welz T Wellbourne-Wood J Kerkhoff E 2014 Orchestration of cell surface proteins by Rab11 Trends Cell Biol 24 407 415 24675420
  14. [16]Grant BD Donaldson JG 2009 Pathways and mechanisms of endocytic recycling Nat Rev Mol Cell Biol 10 597 608 19696797 PMC3038567
  15. [17]Yan Z Wang ZG Segev N Hu S Minshall RD Dull RO Zhang M Malik AB Hu G 2016 Rab11a Mediates Vascular Endothelial-Cadherin Recycling and Controls Endothelial Barrier Function Arterioscler Thromb Vasc Biol 36 339 349 26663395 PMC4732894
  16. [18]Cox D Lee DJ Dale BM Calafat J Greenberg S 2000 A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis Proc Natl Acad Sci USA 97 680 685 10639139 PMC15390
  17. [19]Yang Z Sun D Yan Z Reynolds AB Christman JW Minshall RD Malik AB Zhang Y Hu G 2014 Differential role for p120-catenin in regulation of TLR4 signaling in macrophages J Immunol 193 1931 1941 25015829 PMC4119481
  18. [20]Hu G Ye RD Dinauer MC Malik AB Minshall RD 2008 Neutrophil caveolin-1 expression contributes to mechanism of lung inflammation and injury Am J Physiol Lung Cell Mol Physiol 294 L178 L186 17993589
  19. [21]Kang J Park KH Kim JJ Jo EK Han MK Kim UH 2012 The role of CD38 in Fcγ receptor (FcγR)-mediated phagocytosis in murine macrophages J Biol Chem 287 14502 14514 22396532 PMC3340275
  20. [22]Moon C Lee YJ Park HJ Chong YH Kang JL 2010 N-acetylcysteine inhibits RhoA and promotes apoptotic cell clearance during intense lung inflammation Am J Respir Crit Care Med 181 374 387 19965809
  21. [24]Esmann L Idel C Sarkar A Hellberg L Behnen M Möller S van Zandbergen G Klinger M Köhl J Bussmeyer U Solbach W Laskay T 2010 Phagocytosis of apoptotic cells by neutrophil granulocytes: diminished proinflammatory neutrophil functions in the presence of apoptotic cells J Immunol 184 391 400 19949068
  22. [25]Wu J Yan Z Schwartz DE Yu J Malik AB Hu G 2013 Activation of NLRP3 inflammasome in alveolar macrophages contributes to mechanical stretch-induced lung inflammation and injury J Immunol 190 3590 3599 23436933 PMC3608749
  23. [26]Suzuki T Arumugam P Sakagami T Lachmann N Chalk C Sallese A Abe S Trapnell C Carey B Moritz T Malik P Lutzko C Wood RE Trapnell BC 2014 Pulmonary macrophage transplantation therapy Nature 514 450 454 25274301 PMC4236859
  24. [27]Wang YL Malik AB Sun Y Hu S Reynolds AB Minshall RD Hu G 2011 Innate immune function of the adherens junction protein p120-catenin in endothelial response to endotoxin J Immunol 186 3180 3187 21278343 PMC4277845
  25. [28]D'Alessio FR Tsushima K Aggarwal NR Mock JR Eto Y Garibaldi BT Files DC Avalos CR Rodriguez JV Waickman AT Reddy SP Pearse DB Sidhaye VK Hassoun PM Crow MT King LS 2012 Resolution of experimental lung injury by monocyte-derived inducible nitric oxide synthase J Immunol 189 2234 2245 22844117 PMC3424351
  26. [29]McCubbrey AL Curtis JL 2013 Efferocytosis and lung disease Chest 143 1750 1757 23732585 PMC3673667
  27. [30]Valente AJ Yoshida T Clark RA Delafontaine P Siebenlist U Chandrasekar B 2013 Advanced oxidation protein products induce cardiomyocyte death via Nox2/Rac1/superoxide-dependent TRAF3IP2/JNK signaling Free Radic Biol Med 60 125 135 23453926 PMC3714806
  28. [31]Liu C Xu P Lamouille S Xu J Derynck R 2009 TACE-mediated ectodomain shedding of the type I TGF-beta receptor downregulates TGF-beta signaling Mol Cell 35 26 36 19595713 PMC2740991
  29. [32]Driscoll WS Vaisar T Tang J Wilson CL Raines EW 2013 Macrophage ADAM17 deficiency augments CD36-dependent apoptotic cell uptake and the linked anti-inflammatory phenotype Circ Res 113 52 61 23584255 PMC3693752
  30. [33]Michlewska S Dransfield I Megson IL Rossi AG 2009 Macrophage phagocytosis of apoptotic neutrophils is critically regulated by the opposing actions of pro-inflammatory and anti-inflammatory agents: key role for TNF-α FASEB J 23 844 854 18971259
  31. [34]Rossi AG McCutcheon JC Roy N Chilvers ER Haslett C Dransfield I 1998 Regulation of macrophage phagocytosis of apoptotic cells by cAMP J Immunol 160 3562 3568 9531319
  32. [35]Michlewska S McColl A Rossi AG Megson IL Dransfield I 2007 Clearance of dying cells and autoimmunity Autoimmunity 40 267 273 17516208
  33. [36]Yamamoto K Johnston RB Jr 1984 Dissociation of phagocytosis from stimulation of the oxidative metabolic burst in macrophages J Exp Med 159 405 416 6319532 PMC2187228
  34. [37]Fadok VA Bratton DL Konowal A Freed PW Westcott JY Henson PM 1998 Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF J Clin Invest 101 890 898 9466984 PMC508637
  35. [38]Gruenberg J Maxfield FR 1995 Membrane transport in the endocytic pathway Curr Opin Cell Biol 7 552 563 7495576
  36. [39]Zamora C Canto E Nieto JC Angels Ortiz M Juarez C Vidal S 2012 Functional consequences of CD36 downregulation by TLR signals Cytokine 60 257 265 22795952
  37. [40]Greenberg ME Sun M Zhang R Febbraio M Silverstein R Hazen SL 2006 Oxidized phosphatidylserine-CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells J Exp Med 203 2613 2625 17101731 PMC2118161
  38. [41]Leelahavanichkul A Bocharov AV Kurlander R Baranova IN Vishnyakova TG Souza AC Hu X Doi K Vaisman B Amar M Sviridov D Chen Z Remaley AT Csako G Patterson AP Yuen PS Star RA Eggerman TL 2012 Class B scavenger receptor types I and II and CD36 targeting improves sepsis survival and acute outcomes in mice J Immunol 188 2749 2758 22327076 PMC3859147
  39. [42]Kessler A Tomas E Immler D Meyer HE Zorzano A Eckel J 2000 Rab11 is associated with GLUT4-containing vesicles and redistributes in response to insulin Diabetologia 43 1518 1527 11151761
  40. [43]Thorp E Vaisar T Subramanian M Mautner L Blobel C Tabas I 2011 Shedding of the Mer tyrosine kinase receptor is mediated by ADAM17 protein through a pathway involving reactive oxygen species, protein kinase Cdelta, and p38 mitogen-activated protein kinase (MAPK) J Biol Chem 286 33335 33344 21828049 PMC3190938
  41. [44]Zhao XQ Zhang MW Wang F Zhao YX Li JJ Wang XP Bu PL Yang JM Liu XL Zhang MX Gao F Zhang C Zhang Y 2011 CRP enhances soluble LOX-1 release from macrophages by activating TNF-alpha converting enzyme J Lipid Res 52 923 933 21364202 PMC3072294
  42. [45]Patel BV Wilson MR Takata M 2012 Resolution of acute lung injury and inflammation: a translational mouse model Eur Respir J 39 1162 1170 22005920 PMC3568398

Cited by

Sorted by citations

Authors
Jiang, C., Liu, Z., Hu, R., Bo, L., Minshall, R. D., Malik, A. B., & Hu, G.
Affiliations
  • Sichuan University (CN)
  • University of Illinois Chicago (US)
  • Washington University in St. Louis (US)
Corresponding author
  • Jiang, Chunling
  • Liu, Zheng
  • Bo, Lulong
  • Hu, Guochang
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2017-02
Volume
198
Issue
4
Pages
1660-1672
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.1601495
PMC
PMC5296368
OpenAlex
W2582498840
Cited by
43
References
3
Citations by year
2026: 3 · 2025: 3 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 5 · 2019: 1 · 2018: 2 · 2017: 1
FWCI
1.11
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Pennsylvania
  • University of Illinois at Urbana-Champaign
  • National Heart, Lung, and Blood Institute (P01HL060678, R01HL125356, R01HL104092, R01HL045638)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
Rab11a, efferocytosis, apoptotic neutrophils, macrophages, CD36, ADAM17, phagocytosis, inflammatory lung injury, inflammation resolution, small GTPases
MeSH terms
ADAM17 Protein, rab11 GTP-Binding Proteins, Animals, Bronchoalveolar Lavage Fluid, Cells, Cultured, Inflammation, Macrophages, Mice, Inbred C57BL, Neutrophils, Phagocytosis, Apoptosis, CD36 Antigens, rab GTP-Binding Proteins, Mice, Lung Injury

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