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Phagocytosis of apoptotic inflammatory cells downregulates microglial chemoattractive function and migration of encephalitogenic T cells
Author(s) -
Chan Andrew,
Hummel Vera,
Weilbach Franz X.,
Kieseier Bernd C.,
Gold Ralf
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21029
Subject(s) - phagocytosis , microglia , microbiology and biotechnology , chemokine , inflammation , secretion , apoptosis , biology , immune system , matrix metalloproteinase , ccl2 , immunology , chemistry , endocrinology , biochemistry
Apoptosis of autoaggressive T cells in the central nervous system (CNS) and subsequent phagocytosis by microglia is probably crucial in the rapid resolution of the inflammatory infiltrate in T cell mediated neuroinflammatory diseases. In addition to mere clearance, phagocytosis of apoptotic leukocytes results in the downregulation of different microglial immune functions. Chemoattractive functions of Lewis rat microglia and secretion of chemokines and matrix‐metalloproteinases (MMPs) were investigated after phagocytosis of apoptotic T cells in vitro. In a modified Boyden chamber assay migration of encephalitogenic T cells toward LPS‐stimulated microglial supernatants after phagocytosis of apoptotic thymocytes was reduced by 24.9% in comparison to interaction with viable target cells ( P < 0.001). Phagocytosis of apoptotic cells downregulated CC‐chemokine ligand (CCL)‐5‐secretion by LPS‐stimulated microglia by 66.2% ( P < 0.001), whereas there was only a trend toward decreased CCL2‐secretion. As determined by gelatinase‐zymography, secretion of MMP‐9 by microglia was decreased after phagocytosis of apoptotic cells, whereas MMP‐2 secretion was not altered. These mechanisms may reduce further recruitment of pathogenic inflammatory cells into the CNS‐lesion and thus contribute to the active resolution of the inflammatory infiltrate and termination of the autoimmune attack. © 2006 Wiley‐Liss, Inc.