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Expression of integrin and CD 44 receptors recognising osteopontin in the normal and LPS ‐lesioned rat substantia nigra
Author(s) -
Ailane Sara,
Long Philip,
Jenner Peter,
Rose Sarah
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12231
Subject(s) - osteopontin , substantia nigra , receptor , integrin , microbiology and biotechnology , cd44 , inflammation , chemistry , biology , integrin alpha m , dopaminergic , immunology , endocrinology , biochemistry , cell , dopamine
The multifunctional protein osteopontin ( OPN ) is expressed in the substantia nigra ( SN ) and protects nigral dopaminergic neurones against toxic insult in animal models of Parkinson's disease, although the mechanisms involved are uncertain. In the periphery, OPN regulates inflammatory processes by interacting with integrin and CD 44 receptors but the presence and distribution of these sites in SN is unknown. We investigated the expression of integrin receptor subunits and CD 44 receptors in the normal SN and after induction of inflammation by lipopolysaccharide ( LPS ), and their interaction with OPN . In normal rat SN , integrin α v , β 3 and β 1 , and CD 44, receptors were expressed on neurones including TH ‐positive cells but not on glia. LPS administration induced a loss of TH ‐positive neurones in SN and increased expression of glial cells as shown by GFAP , OX ‐6 and ED ‐1 immunoreactivity. In LPS ‐lesioned SN , there was up‐regulation of the expression of integrin β 3 and CD 44 receptors. Co‐localisation studies showed that this related to their increased expression on OX ‐6‐, ED ‐1‐ and GFAP ‐positive cells. Furthermore, OPN interacted with integrin and CD 44 receptors in the normal rat SN as demonstrated by co‐immunoprecipitation and pull‐down techniques. These data show that integrin and CD 44 receptors are present on neurones in normal rat SN and that they are up‐regulated on glial cells following LPS ‐mediated inflammation in SN , suggesting that they are functionally important in the inflammatory process. The interaction of OPN with these receptors suggests a role in the neuroprotective effect of this protein in the LPS model of Parkinson's disease.