Phagocytosis of apoptotic inflammatory cells by microglia and its therapeutic implications: Termination of CNS autoimmune inflammation and modulation by interferon‐beta

GLIA - Tập 43 Số 3 - Trang 231-242 - 2003
Andrew Chan1, Rosanne Séguin2, Tim Magnus3, Christina Papadimitriou3, Klaus V. Toyka3, Jack P. Antel2, Ralf Gold3
1Department of Neurology, Julius-Maximilians-University, Würzburg, Germany
2Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada.
3Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, Julius-Maximilians University, Würzburg, Germany.

Tóm tắt

AbstractApoptosis of autoaggressive T‐cells in the CNS is an effective, noninflammatory mechanism for the resolution of T‐cell infiltrates, contributing to clinical recovery in T‐cell‐mediated neuroinflammatory diseases. The clearance of apoptotic leukocytes by tissue‐specific phagocytes is critical in the resolution of the inflammatory infiltrate and leads to a profound downregulation of phagocyte immune functions. Adult human microglia from surgically removed normal brain tissue was used in a standardized, light‐microscopic in vitro phagocytosis assay of apoptotic autologous peripheral blood‐derived mononuclear cells (MNCs). Microglia from five different patients had a high capacity for the uptake of apoptotic MNCs in contrast to nonapoptotic target cells with the phagocytosis rate for nonapoptotic MNCs amounting to only 61.6% of the apoptotic MNCs. A newly described phosphatidylserine receptor, critical in the phagocytosis of apoptotic cells by macrophages, is also expressed at similar levels on human microglia. The effects of the therapeutically used immunomodulatory agent interferon‐beta (IFNβ) were investigated using Lewis rat microglia and apoptotic, encephalitogenic, myelin basic protein‐specific autologous T‐cells. Also, rat microglia had a high capacity to phagocytose apoptotic T‐cells specifically. IFNβ increased the phagocytosis of apoptotic T‐cells to 36.8% above the untreated controls. The enhanced phagocytic activity was selective for apoptotic T‐cells and was not mediated by increased IL‐10 secretion. Apoptotic inflammatory cells may be efficiently and rapidly removed by microglial cells in the autoimmune‐inflamed human CNS. The in vitro increase of phagocytosis by IFNβ merits further investigations whether this mechanism could also be therapeutically exploited. © 2003 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.1002/glia.1106

10.1007/s004010051028

10.1002/glia.1112

10.1002/(SICI)1098-1136(199609)18:1<1::AID-GLIA1>3.0.CO;2-6

10.1002/(SICI)1098-1136(20000215)29:4<293::AID-GLIA1>3.0.CO;2-A

10.1212/WNL.55.10.1497

10.1002/(SICI)1097-4547(19991015)58:2<214::AID-JNR2>3.0.CO;2-6

10.1002/1098-1136(20010101)33:1<87::AID-GLIA1008>3.0.CO;2-S

10.1016/S0165-5728(02)00433-2

10.1093/jnen/61.3.237

10.4049/jimmunol.148.7.2207

10.1038/35011084

10.1172/JCI200114122

10.1038/sj.cdd.4400856

10.1002/jlb.67.2.174

10.1046/j.1365-2141.2000.01805.x

10.1016/S0166-2236(97)01079-5

10.4049/jimmunol.159.2.919

10.1038/35085094

10.4049/jimmunol.164.12.6520

10.1083/jcb.200108080

10.1093/brain/120.5.865

Hughes J, 1997, Human glomerular mesangial cell phagocytosis of apoptotic neutrophils: mediation by a novel CD36‐independent vitronectin receptor thrombospondin recognition mechanism that is uncoupled from chemokine secretion, J Immunol, 158, 4389, 10.4049/jimmunol.158.9.4389

10.1016/S0140-6736(99)00622-4

10.1016/S0301-0082(00)00060-5

10.1001/archneur.58.1.91

10.4049/jimmunol.167.9.5004

10.1016/S0165-5728(02)00212-6

10.1016/S0165-5728(01)00289-2

10.1007/s004010050763

10.1093/brain/117.6.1311

10.1002/glia.1103

10.1016/S0165-5728(98)00145-3

10.1016/0162-3109(95)00005-E

10.1038/sj.cdd.4400407

10.1016/S0733-8619(05)70007-4

10.1212/WNL.50.5.1294

Ruuls SR, 1996, The length of treatment determines whether IFN‐β prevents or aggravates experimental autoimmune encephalomyelitis in Lewis rats, J Immunol, 157, 5721, 10.4049/jimmunol.157.12.5721

10.1038/343170a0

10.1038/nri957

10.1093/brain/123.7.1431

10.1002/jnr.1128

10.1002/glia.10154

10.1016/0022-1759(95)00072-I

Yong VW, 1992, Protocols for neural cell culture, 81

10.1212/WNL.51.3.682

10.1212/WNL.54.2.485

Thông tin
Thông tin xuất bản

GLIA

Tập 43 Số 3

231-242

Thông tin tác giả