Antigen Presentation by Macrophages is Enhanced by the Uptake of Necrotic, but Not Apoptotic, Cells

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2002 Mar 6

PMID 11876743

Citations 29

Authors

R N Barker

L-P Erwig

K S K Hill

A Devine

W P Pearce

A J Rees

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to determine whether phagocytosis of necrotic or apoptotic cells affects antigen presentation by murine bone marrow-derived macrophages. After uptake of necrotic neutrophils, macrophages were able to stimulate significantly higher T cell proliferation in vitro against both the recall antigen albumin and the mitogen concanavalin A. No such effect was seen following phagocytosis of apoptotic neutrophils. Flow cytometry revealed that, within 4h of ingestion, macrophages that had taken up the necrotic cells expressed higher levels of CD40 than those that had phagocytosed apoptotic cells. Macrophage cultures pulsed with apoptotic, but not necrotic, neutrophils contained higher levels of transforming growth factor beta1, but lower concentrations of tumour necrosis factor alpha, compared to untreated controls. Our interpretation of these results is that macrophages that have taken up necrotic neutrophils co-stimulate T cells with greater efficiency due to rapid CD40 up-regulation, whereas those that have ingested apoptotic cells are not only ineffective in co-stimulation, but also secrete inhibitory cytokine.

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References

McDonald P, Fadok V, Bratton D, Henson P . Transcriptional and translational regulation of inflammatory mediator production by endogenous TGF-beta in macrophages that have ingested apoptotic cells. J Immunol. 1999; 163(11):6164-72. View

Perry F, Barker R, Mazza G, Day M, Wells A, Shen C . Autoreactive T cell specificity in autoimmune hemolytic anemia of the NZB mouse. Eur J Immunol. 1996; 26(1):136-41. DOI: 10.1002/eji.1830260121. View

Matzinger P . Tolerance, danger, and the extended family. Annu Rev Immunol. 1994; 12:991-1045. DOI: 10.1146/annurev.iy.12.040194.005015. View

Gallucci S, Lolkema M, Matzinger P . Natural adjuvants: endogenous activators of dendritic cells. Nat Med. 1999; 5(11):1249-55. DOI: 10.1038/15200. View

Letterio J, Roberts A . TGF-beta: a critical modulator of immune cell function. Clin Immunol Immunopathol. 1997; 84(3):244-50. DOI: 10.1006/clin.1997.4409. View

Durie F, Foy T, Masters S, Laman J, Noelle R . The role of CD40 in the regulation of humoral and cell-mediated immunity. Immunol Today. 1994; 15(9):406-11. DOI: 10.1016/0167-5699(94)90269-0. View

Savill J, Wyllie A, Henson J, Walport M, Henson P, Haslett C . Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. J Clin Invest. 1989; 83(3):865-75. PMC: 303760. DOI: 10.1172/JCI113970. View

Reiter I, Krammer B, Schwamberger G . Cutting edge: differential effect of apoptotic versus necrotic tumor cells on macrophage antitumor activities. J Immunol. 1999; 163(4):1730-2. View

Meagher L, Savill J, Baker A, Fuller R, Haslett C . Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane B2. J Leukoc Biol. 1992; 52(3):269-73. View

10.

Murray H . Interferon-gamma, the activated macrophage, and host defense against microbial challenge. Ann Intern Med. 1988; 108(4):595-608. DOI: 10.7326/0003-4819-108-4-595. View

11.

Erwig L, Kluth D, Walsh G, Rees A . Initial cytokine exposure determines function of macrophages and renders them unresponsive to other cytokines. J Immunol. 1998; 161(4):1983-8. View

12.

DiPietro L, Burdick M, Low Q, Kunkel S, Strieter R . MIP-1alpha as a critical macrophage chemoattractant in murine wound repair. J Clin Invest. 1998; 101(8):1693-8. PMC: 508751. DOI: 10.1172/JCI1020. View

13.

NORTH R . The concept of the activated macrophage. J Immunol. 1978; 121(3):806-9. View

14.

Fadok V, Bratton D, Konowal A, Freed P, Westcott J, Henson P . 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. 1998; 101(4):890-8. PMC: 508637. DOI: 10.1172/JCI1112. View

15.

Fadok V, Bratton D, Guthrie L, Henson P . Differential effects of apoptotic versus lysed cells on macrophage production of cytokines: role of proteases. J Immunol. 2001; 166(11):6847-54. DOI: 10.4049/jimmunol.166.11.6847. View

16.

June C, Bluestone J, Nadler L, Thompson C . The B7 and CD28 receptor families. Immunol Today. 1994; 15(7):321-31. DOI: 10.1016/0167-5699(94)90080-9. View

17.

Vandenbark A, Offner H, Reshef T, Fritz R, Chou C, Cohen I . Specificity of T lymphocyte lines for peptides of myelin basic protein. J Immunol. 1985; 135(1):229-33. View

18.

Goerdt S, Orfanos C . Other functions, other genes: alternative activation of antigen-presenting cells. Immunity. 1999; 10(2):137-42. DOI: 10.1016/s1074-7613(00)80014-x. View

19.

Erwig L, Gordon S, Walsh G, Rees A . Previous uptake of apoptotic neutrophils or ligation of integrin receptors downmodulates the ability of macrophages to ingest apoptotic neutrophils. Blood. 1999; 93(4):1406-12. View

20.

Janeway Jr C . Presidential Address to The American Association of Immunologists. The road less traveled by: the role of innate immunity in the adaptive immune response. J Immunol. 1998; 161(2):539-44. View