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Differential effects of albumin on microglia and macrophages; implications for neurodegeneration following blood–brain barrier damage
Author(s) -
Hooper Claudie,
PinteauxJones Fleur,
Fry Victoria A. H.,
Sevastou Ioanna G.,
Baker David,
Heales Simon J.,
Pocock Jennifer M.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.05953.x
Subject(s) - microglia , albumin , tumor necrosis factor alpha , neuroinflammation , extracellular , blood–brain barrier , neuroglia , biology , neurodegeneration , chemistry , biochemistry , microbiology and biotechnology , inflammation , endocrinology , immunology , medicine , central nervous system , disease
J. Neurochem . (2009) 109 , 694–705. Abstract Microglial activation by blood‐borne factors following blood–brain barrier damage may play a significant role in subsequent neuropathogenesis of several neurodegenerative diseases. Exposure of primary cultured rat brain microglia to pure, fatty acid‐ and lipid‐deficient rat serum albumin or fraction V, (fatty acid and lipid‐containing rat serum albumin), caused inducible nitric oxide synthase (iNOS) expression, glutamate release, tumour necrosis factor alpha (TNFα) and transforming growth factor‐beta1 release. iNOS expression was attenuated by the MAPK/extracellular signal‐regulated kinase pathway inhibitor U0126 and the phosphorylated forms of extracellular signal‐regulated kinase 1 and 2 were detectable in microglia treated with albumin or fraction V. Glutamate release was prevented by l ‐α‐aminoadipate and glutathione levels in microglia rose on exposure to albumin. Conditioned medium from microglia exposed to albumin or fraction V was neurotoxic. Peripheral macrophages were resistant to the effects of albumin but both microglia and macrophages responded to lipopolysaccharide, which induced interleukin‐1 beta and tumour necrosis factor alpha release, cyclooxygenase‐2 and iNOS expression in both cell types, indicating a discrete desensitised pathway in macrophages for albumin which was not desensitised in microglia. Thus, exposure of microglia in the brain to albumin may contribute to neuronal damage following blood–brain barrier breakdown and point to resident microglia rather than infiltrating macrophages as therapeutic targets.