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Myelin‐phagocytosing macrophages in isolated sciatic and optic nerves reveal a unique reactive phenotype
Author(s) -
van Rossum Denise,
Hilbert Sören,
Straßenburg Silke,
Hanisch Uwekarsten,
Brück Wolfgang
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20611
Subject(s) - biology , cd80 , microbiology and biotechnology , myelin , chemokine , immunology , microglia , proinflammatory cytokine , sciatic nerve , myelin basic protein , inflammation , central nervous system , neuroscience , cd40 , in vitro , cytotoxic t cell , anatomy , biochemistry
Macrophages are key effectors in demyelinating diseases of the central and peripheral nervous system by phagocytosing myelin and releasing immunoregulatory mediators. Here, we report on a distinct, a priori anti‐inflammatory reaction of macrophages phagocytosing myelin upon contact with damaged nerve tissue. Macrophages rapidly invaded peripheral (sciatic) and central (optic) nerve tissues in vitro , readily incorporated myelin and expressed high levels of phagocytosis‐associated molecules (e.g., Fc and scavenger receptors). In contrast, factors involved in antigen presentation (MHC class‐II, CD80, CD86) revealed only a restricted expression. In parallel, a highly ordered appearance of cytokines and chemokines was detected. IL‐10, IL‐6, CCL22, and CXCL1 were immediately but transiently induced, whereas CCL2, CCL11, and TGFβ revealed more persisting levels. Such a profile would attract neutrophils, monocytes/macrophages, and Th2 cells as well as bias for a Th2‐supporting environment. Importantly, proinflammatory/Th1‐supporting factors, such as TNFα, IL‐12p70, CCL3, and CCL5, were not induced. Still the simultaneous presence of TGFβ and IL‐6 could assist Th17 development, further depending on yet not present IL‐23. The release pattern was clearly distinct from reactive phenotypes induced in isolated macrophages and microglia upon treatment with IL‐4, IL‐13, bacterial lipopolysaccharide, IFNγ, or purified myelin. Nerve‐exposed macrophages thus commit to a unique functional orientation. © 2007 Wiley‐Liss, Inc.