PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
 
J Exp Med. 1995 November 1; 182(5): 1597–1601.
PMCID: PMC2192221

Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes

Abstract

The appearance of phosphatidylserine (PS) on the cell surface during apoptosis in thymocytes and cytotoxic T lymphocyte cell lines provokes PS-dependent recognition by activated macrophages. Flow cytometric analysis of transbilayer lipid movements in T lymphocytes undergoing apoptosis reveals that downregulation of the adenosine triphosphate- dependent amino-phospholipid translocase and activation of a nonspecific lipid scramblase are responsible for PS reaching the surface from its intracellular location. Both mechanisms are expressed at the same time, and precede DNA degradation, zeiosis, and cell lysis in the apoptotic pathway.

Full Text

The Full Text of this article is available as a PDF (719K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. [PubMed]
  • Hall SE, Savill JS, Henson PM, Haslett C. Apoptotic neutrophils are phagocytosed by fibroblasts with participation of the fibroblast vitronectin receptor and involvement of a mannose/fucose-specific lectin. J Immunol. 1994 Oct 1;153(7):3218–3227. [PubMed]
  • Fadok VA, Savill JS, Haslett C, Bratton DL, Doherty DE, Campbell PA, Henson PM. Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J Immunol. 1992 Dec 15;149(12):4029–4035. [PubMed]
  • Savill J, Fadok V, Henson P, Haslett C. Phagocyte recognition of cells undergoing apoptosis. Immunol Today. 1993 Mar;14(3):131–136. [PubMed]
  • Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992 Apr 1;148(7):2207–2216. [PubMed]
  • Pradhan D, Williamson P, Schlegel RA. Phosphatidylserine vesicles inhibit phagocytosis of erythrocytes with a symmetric transbilayer distribution of phospholipids. Mol Membr Biol. 1994 Jul-Sep;11(3):181–187. [PubMed]
  • Op den Kamp JA. Lipid asymmetry in membranes. Annu Rev Biochem. 1979;48:47–71. [PubMed]
  • Bevers EM, Comfurius P, van Rijn JL, Hemker HC, Zwaal RF. Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. Eur J Biochem. 1982 Feb;122(2):429–436. [PubMed]
  • Rosing J, van Rijn JL, Bevers EM, van Dieijen G, Comfurius P, Zwaal RF. The role of activated human platelets in prothrombin and factor X activation. Blood. 1985 Feb;65(2):319–332. [PubMed]
  • Williamson P, Mattocks K, Schlegel RA. Merocyanine 540, a fluorescent probe sensitive to lipid packing. Biochim Biophys Acta. 1983 Jul 27;732(2):387–393. [PubMed]
  • Schlegel RA, Stevens M, Lumley-Sapanski K, Williamson P. Altered lipid packing identifies apoptotic thymocytes. Immunol Lett. 1993 Jun;36(3):283–288. [PubMed]
  • Schwartz LM, Smith SW, Jones ME, Osborne BA. Do all programmed cell deaths occur via apoptosis? Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):980–984. [PubMed]
  • Bogdanov A, Verhoven B, Schlegel RA, Williamson P. Asymmetry in trans-bilayer lateral pressure may drive expansion of the secretion fusion pore. Biochem Soc Trans. 1993 May;21(2):271–275. [PubMed]
  • Odaka C, Kizaki H, Tadakuma T. T cell receptor-mediated DNA fragmentation and cell death in T cell hybridomas. J Immunol. 1990 Mar 15;144(6):2096–2101. [PubMed]
  • Shi YF, Szalay MG, Paskar L, Sahai BM, Boyer M, Singh B, Green DR. Activation-induced cell death in T cell hybridomas is due to apoptosis. Morphologic aspects and DNA fragmentation. J Immunol. 1990 May 1;144(9):3326–3333. [PubMed]
  • Iseki R, Mukai M, Iwata M. Regulation of T lymphocyte apoptosis. Signals for the antagonism between activation- and glucocorticoid-induced death. J Immunol. 1991 Dec 15;147(12):4286–4292. [PubMed]
  • Sun XM, Snowden RT, Skilleter DN, Dinsdale D, Ormerod MG, Cohen GM. A flow-cytometric method for the separation and quantitation of normal and apoptotic thymocytes. Anal Biochem. 1992 Aug 1;204(2):351–356. [PubMed]
  • Dive C, Gregory CD, Phipps DJ, Evans DL, Milner AE, Wyllie AH. Analysis and discrimination of necrosis and apoptosis (programmed cell death) by multiparameter flow cytometry. Biochim Biophys Acta. 1992 Feb 3;1133(3):275–285. [PubMed]
  • Devaux PF. Phospholipid flippases. FEBS Lett. 1988 Jul 4;234(1):8–12. [PubMed]
  • Verhoven B, Schlegel RA, Williamson P. Rapid loss and restoration of lipid asymmetry by different pathways in resealed erythrocyte ghosts. Biochim Biophys Acta. 1992 Feb 17;1104(1):15–23. [PubMed]
  • Comfurius P, Senden JM, Tilly RH, Schroit AJ, Bevers EM, Zwaal RF. Loss of membrane phospholipid asymmetry in platelets and red cells may be associated with calcium-induced shedding of plasma membrane and inhibition of aminophospholipid translocase. Biochim Biophys Acta. 1990 Jul 24;1026(2):153–160. [PubMed]
  • Williamson P, Kulick A, Zachowski A, Schlegel RA, Devaux PF. Ca2+ induces transbilayer redistribution of all major phospholipids in human erythrocytes. Biochemistry. 1992 Jul 14;31(27):6355–6360. [PubMed]
  • Bevers EM, Comfurius P, Zwaal RF. Changes in membrane phospholipid distribution during platelet activation. Biochim Biophys Acta. 1983 Dec 7;736(1):57–66. [PubMed]
  • Williamson P, Algarin L, Bateman J, Choe HR, Schlegel RA. Phospholipid asymmetry in human erythrocyte ghosts. J Cell Physiol. 1985 May;123(2):209–214. [PubMed]
  • Zwaal RF, Comfurius P, Bevers EM. Mechanism and function of changes in membrane-phospholipid asymmetry in platelets and erythrocytes. Biochem Soc Trans. 1993 May;21(2):248–253. [PubMed]
  • Brunner T, Mogil RJ, LaFace D, Yoo NJ, Mahboubi A, Echeverri F, Martin SJ, Force WR, Lynch DH, Ware CF, et al. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature. 1995 Feb 2;373(6513):441–444. [PubMed]
  • Dhein J, Walczak H, Bäumler C, Debatin KM, Krammer PH. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) Nature. 1995 Feb 2;373(6513):438–441. [PubMed]
  • Ju ST, Panka DJ, Cui H, Ettinger R, el-Khatib M, Sherr DH, Stanger BZ, Marshak-Rothstein A. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature. 1995 Feb 2;373(6513):444–448. [PubMed]
  • Squìer MK, Miller AC, Malkinson AM, Cohen JJ. Calpain activation in apoptosis. J Cell Physiol. 1994 May;159(2):229–237. [PubMed]
  • Lagasse E, Weissman IL. bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages. J Exp Med. 1994 Mar 1;179(3):1047–1052. [PMC free article] [PubMed]
  • Cohen GM, Sun XM, Snowden RT, Dinsdale D, Skilleter DN. Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J. 1992 Sep 1;286(Pt 2):331–334. [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press