The present address of David Baker is the Neurosciences Centre, Institute of Cell and Molecular Sciences, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
Differential effects of albumin on microglia and macrophages; implications for neurodegeneration following blood–brain barrier damage
Version of Record online: 2 FEB 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 109, Issue 3, pages 694–705, May 2009
How to Cite
Hooper, C., Pinteaux-Jones, F., Fry, V. A. H., Sevastou, I. G., Baker, D., Heales, S. J. and Pocock, J. M. (2009), Differential effects of albumin on microglia and macrophages; implications for neurodegeneration following blood–brain barrier damage. Journal of Neurochemistry, 109: 694–705. doi: 10.1111/j.1471-4159.2009.05953.x
- Issue online: 7 APR 2009
- Version of Record online: 2 FEB 2009
- Received September 30, 2008; revised manuscript received January 16, 2009; accepted January 16, 2009.
- blood–brain barrier breakdown;
- neurodegenerative disease;
J. Neurochem. (2009) 109, 694–705.
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.