Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis

Marie Robertson, Lars Peter Erwig, Janet Mary Liversidge, John Vincent Forrester, Andrew Jackson Rees, A. D. Dick

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

PURPOSE. Macrophages infiltrating an inflamed or injured tissue undergo development of coordinated sets of properties that contribute to tissue damage, repair, and remodeling. The purpose of this study was to determine whether macrophages isolated from normal or inflamed retina are programmed to a distinct set of properties and to examine whether the development of experimental autoimmune uveoretinitis (EAU) affects macrophage function.

METHODS. EAU was induced in Lewis rats, and a retina-derived macrophage-enriched population was generated by density centrifugation during the prepeak, peak, and resolution phases of the disease. Cell surface phenotype was assessed by two- and three-color flow cytometry, and function was determined in vitro by nitric oxide (NO) production, with or without further cytokine stimulation or by immunohistochemistry to determine expression of P-glucuronidase, nitric oxide synthase (NOS)-2, and nitrotyrosine.

RESULTS. Myeloid-derived cells from normal retina were programmed similar to TGF-beta-stimulated uncommitted bone-marrow-derived macrophages (BMDMs). Contrary to BMDM behavior, retina-isolated macrophages displayed distinct properties and phenotype at different phases of the disease course and remained resistant throughout, to further cytokine challenge in vitro. During peak disease, retina-isolated macrophages had characteristics of IFN-gamma/TNF-alpha a primed cells (nitrotyrosine positive and NO producing). Despite equivalent numbers of macrophages during resolution, their function reverted to characteristics of TGF-beta primed cells (beta-glucuronidase positive).

CONCLUSIONS. Resident retinal myeloid-derived cells are primed and are resistant to further cytokine stimulation, and, similar to macrophages derived during EAU recovery, behave operationally as though TGF-beta primed. During peak inflammation, infiltrating macrophages adapt to concurrent hierarchical Th1 T-cell response (IFN-gamma/TNF-alpha), generating NO. The results provide evidence of in vivo programming of macrophages within the retina.

Original languageEnglish
Pages (from-to)2250-2257
Number of pages7
JournalInvestigative Ophthalmology & Visual Science
Volume43
Issue number7
Publication statusPublished - 2002

Keywords

  • EXPERIMENTAL AUTOIMMUNE UVEORETINITIS
  • NITRIC-OXIDE SYNTHASE
  • ENDOTOXIN-INDUCED UVEITIS
  • CENTRAL-NERVOUS-SYSTEM
  • ALTERNATIVE ACTIVATION
  • ANTIGEN PRESENTATION
  • TNF-ALPHA
  • RAT
  • CELLS
  • EXPRESSION

Cite this

Robertson, M., Erwig, L. P., Liversidge, J. M., Forrester, J. V., Rees, A. J., & Dick, A. D. (2002). Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis. Investigative Ophthalmology & Visual Science, 43(7), 2250-2257.

Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis. / Robertson, Marie; Erwig, Lars Peter; Liversidge, Janet Mary; Forrester, John Vincent; Rees, Andrew Jackson; Dick, A. D.

In: Investigative Ophthalmology & Visual Science, Vol. 43, No. 7, 2002, p. 2250-2257.

Research output: Contribution to journalArticle

Robertson, M, Erwig, LP, Liversidge, JM, Forrester, JV, Rees, AJ & Dick, AD 2002, 'Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis', Investigative Ophthalmology & Visual Science, vol. 43, no. 7, pp. 2250-2257.
Robertson, Marie ; Erwig, Lars Peter ; Liversidge, Janet Mary ; Forrester, John Vincent ; Rees, Andrew Jackson ; Dick, A. D. / Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis. In: Investigative Ophthalmology & Visual Science. 2002 ; Vol. 43, No. 7. pp. 2250-2257.
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abstract = "PURPOSE. Macrophages infiltrating an inflamed or injured tissue undergo development of coordinated sets of properties that contribute to tissue damage, repair, and remodeling. The purpose of this study was to determine whether macrophages isolated from normal or inflamed retina are programmed to a distinct set of properties and to examine whether the development of experimental autoimmune uveoretinitis (EAU) affects macrophage function.METHODS. EAU was induced in Lewis rats, and a retina-derived macrophage-enriched population was generated by density centrifugation during the prepeak, peak, and resolution phases of the disease. Cell surface phenotype was assessed by two- and three-color flow cytometry, and function was determined in vitro by nitric oxide (NO) production, with or without further cytokine stimulation or by immunohistochemistry to determine expression of P-glucuronidase, nitric oxide synthase (NOS)-2, and nitrotyrosine.RESULTS. Myeloid-derived cells from normal retina were programmed similar to TGF-beta-stimulated uncommitted bone-marrow-derived macrophages (BMDMs). Contrary to BMDM behavior, retina-isolated macrophages displayed distinct properties and phenotype at different phases of the disease course and remained resistant throughout, to further cytokine challenge in vitro. During peak disease, retina-isolated macrophages had characteristics of IFN-gamma/TNF-alpha a primed cells (nitrotyrosine positive and NO producing). Despite equivalent numbers of macrophages during resolution, their function reverted to characteristics of TGF-beta primed cells (beta-glucuronidase positive).CONCLUSIONS. Resident retinal myeloid-derived cells are primed and are resistant to further cytokine stimulation, and, similar to macrophages derived during EAU recovery, behave operationally as though TGF-beta primed. During peak inflammation, infiltrating macrophages adapt to concurrent hierarchical Th1 T-cell response (IFN-gamma/TNF-alpha), generating NO. The results provide evidence of in vivo programming of macrophages within the retina.",
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TY - JOUR

T1 - Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis

AU - Robertson, Marie

AU - Erwig, Lars Peter

AU - Liversidge, Janet Mary

AU - Forrester, John Vincent

AU - Rees, Andrew Jackson

AU - Dick, A. D.

PY - 2002

Y1 - 2002

N2 - PURPOSE. Macrophages infiltrating an inflamed or injured tissue undergo development of coordinated sets of properties that contribute to tissue damage, repair, and remodeling. The purpose of this study was to determine whether macrophages isolated from normal or inflamed retina are programmed to a distinct set of properties and to examine whether the development of experimental autoimmune uveoretinitis (EAU) affects macrophage function.METHODS. EAU was induced in Lewis rats, and a retina-derived macrophage-enriched population was generated by density centrifugation during the prepeak, peak, and resolution phases of the disease. Cell surface phenotype was assessed by two- and three-color flow cytometry, and function was determined in vitro by nitric oxide (NO) production, with or without further cytokine stimulation or by immunohistochemistry to determine expression of P-glucuronidase, nitric oxide synthase (NOS)-2, and nitrotyrosine.RESULTS. Myeloid-derived cells from normal retina were programmed similar to TGF-beta-stimulated uncommitted bone-marrow-derived macrophages (BMDMs). Contrary to BMDM behavior, retina-isolated macrophages displayed distinct properties and phenotype at different phases of the disease course and remained resistant throughout, to further cytokine challenge in vitro. During peak disease, retina-isolated macrophages had characteristics of IFN-gamma/TNF-alpha a primed cells (nitrotyrosine positive and NO producing). Despite equivalent numbers of macrophages during resolution, their function reverted to characteristics of TGF-beta primed cells (beta-glucuronidase positive).CONCLUSIONS. Resident retinal myeloid-derived cells are primed and are resistant to further cytokine stimulation, and, similar to macrophages derived during EAU recovery, behave operationally as though TGF-beta primed. During peak inflammation, infiltrating macrophages adapt to concurrent hierarchical Th1 T-cell response (IFN-gamma/TNF-alpha), generating NO. The results provide evidence of in vivo programming of macrophages within the retina.

AB - PURPOSE. Macrophages infiltrating an inflamed or injured tissue undergo development of coordinated sets of properties that contribute to tissue damage, repair, and remodeling. The purpose of this study was to determine whether macrophages isolated from normal or inflamed retina are programmed to a distinct set of properties and to examine whether the development of experimental autoimmune uveoretinitis (EAU) affects macrophage function.METHODS. EAU was induced in Lewis rats, and a retina-derived macrophage-enriched population was generated by density centrifugation during the prepeak, peak, and resolution phases of the disease. Cell surface phenotype was assessed by two- and three-color flow cytometry, and function was determined in vitro by nitric oxide (NO) production, with or without further cytokine stimulation or by immunohistochemistry to determine expression of P-glucuronidase, nitric oxide synthase (NOS)-2, and nitrotyrosine.RESULTS. Myeloid-derived cells from normal retina were programmed similar to TGF-beta-stimulated uncommitted bone-marrow-derived macrophages (BMDMs). Contrary to BMDM behavior, retina-isolated macrophages displayed distinct properties and phenotype at different phases of the disease course and remained resistant throughout, to further cytokine challenge in vitro. During peak disease, retina-isolated macrophages had characteristics of IFN-gamma/TNF-alpha a primed cells (nitrotyrosine positive and NO producing). Despite equivalent numbers of macrophages during resolution, their function reverted to characteristics of TGF-beta primed cells (beta-glucuronidase positive).CONCLUSIONS. Resident retinal myeloid-derived cells are primed and are resistant to further cytokine stimulation, and, similar to macrophages derived during EAU recovery, behave operationally as though TGF-beta primed. During peak inflammation, infiltrating macrophages adapt to concurrent hierarchical Th1 T-cell response (IFN-gamma/TNF-alpha), generating NO. The results provide evidence of in vivo programming of macrophages within the retina.

KW - EXPERIMENTAL AUTOIMMUNE UVEORETINITIS

KW - NITRIC-OXIDE SYNTHASE

KW - ENDOTOXIN-INDUCED UVEITIS

KW - CENTRAL-NERVOUS-SYSTEM

KW - ALTERNATIVE ACTIVATION

KW - ANTIGEN PRESENTATION

KW - TNF-ALPHA

KW - RAT

KW - CELLS

KW - EXPRESSION

M3 - Article

VL - 43

SP - 2250

EP - 2257

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 7

ER -