Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys.
Identifieur interne : 000596 ( Ncbi/Checkpoint ); précédent : 000595; suivant : 000597Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys.
Auteurs : J. Miklossy [Canada] ; D D Doudet ; C. Schwab ; S. Yu ; E G Mcgeer ; P L McgeerSource :
- Experimental neurology [ 0014-4886 ] ; 2006.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Adult, Aged, Aged, 80 and over, Animals, Astrocytes (metabolism), Case-Control Studies, Cell Count (methods), Disease Models, Animal, Female, Humans, Immunohistochemistry (methods), Inflammation (etiology), Inflammation (metabolism), Inflammation (pathology), Intercellular Adhesion Molecule-1 (physiology), Leukocytes (pathology), Lymphocyte Function-Associated Antigen-1 (metabolism), MPTP Poisoning (chemically induced), MPTP Poisoning (metabolism), Macaca mulatta, Male, Middle Aged, Parkinson Disease (complications), Parkinson Disease (metabolism), Parkinson Disease (pathology), Postmortem Changes, Substantia Nigra (cytology), Substantia Nigra (drug effects).
- MESH :
- chemical , metabolism : Lymphocyte Function-Associated Antigen-1.
- chemical , physiology : Intercellular Adhesion Molecule-1.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemically induced : MPTP Poisoning.
- complications : Parkinson Disease.
- cytology : Substantia Nigra.
- drug effects : Substantia Nigra.
- etiology : Inflammation.
- metabolism : Astrocytes, Inflammation, MPTP Poisoning, Parkinson Disease.
- methods : Cell Count, Immunohistochemistry.
- pathology : Inflammation, Leukocytes, Parkinson Disease.
- Adult, Aged, Aged, 80 and over, Animals, Case-Control Studies, Disease Models, Animal, Female, Humans, Macaca mulatta, Male, Middle Aged, Postmortem Changes.
Abstract
It has been established that neuroinflammation is present in the substantia nigra (SN) of Parkinson disease (PD) cases but the factors responsible are as yet unknown. One contributing protein may be the intercellular adhesion molecule-1 (ICAM-1, CD54). ICAM-1 with its counter receptor, the lymphocyte function-associated antigen 1 (LFA-1) is known to play a key role in inflammatory processes and in T-cell mediated host defense mechanisms. We detected large numbers of ICAM-1-positive reactive astrocytes in the SN of a series of 14 patients with neuropathologically confirmed PD, including 3 of familial origin, compared with 11 age-matched controls. In PD SN, these ICAM-1-positive reactive astrocytes were particularly concentrated around many residual neurons in areas of heavy neuronal loss and extracellular melanin accumulation. LFA-1-positive reactive microglia gathered in areas of intense ICAM-1 expression, and LFA-1-positive leukocytes were identified infiltrating the tissue. Double immunostaining for ICAM-1 and LFA-1 revealed aggregates of reactive microglia embedded in areas of diffuse ICAM-1. Leukocyte counts were 5 fold higher in PD SN compared to controls (P < 0.001). Similar over-expression of ICAM-1 was found in monkeys that had been exposed to MPTP from 5.5 to 14 years previously compared with control monkeys. The presence of ICAM-1-positive reactive astrocytes in Parkinson disease and MPTP-treated monkeys is indicative of a sustained inflammatory process and suggests that antiinflammatory agents may have a place in PD therapy.
DOI: 10.1016/j.expneurol.2005.10.034
PubMed: 16336966
Affiliations:
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Miklossy</name><affiliation wicri:level="1"><nlm:affiliation>Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T1Z3.</nlm:affiliation><country>Canada</country><wicri:regionArea>Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Doudet, D D" sort="Doudet, D D" uniqKey="Doudet D" first="D D" last="Doudet">D D Doudet</name></author><author><name sortKey="Schwab, C" sort="Schwab, C" uniqKey="Schwab C" first="C" last="Schwab">C. Schwab</name></author><author><name sortKey="Yu, S" sort="Yu, S" uniqKey="Yu S" first="S" last="Yu">S. Yu</name></author><author><name sortKey="Mcgeer, E G" sort="Mcgeer, E G" uniqKey="Mcgeer E" first="E G" last="Mcgeer">E G Mcgeer</name></author><author><name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P L" last="Mcgeer">P L Mcgeer</name></author></analytic><series><title level="j">Experimental neurology</title><idno type="ISSN">0014-4886</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Astrocytes (metabolism)</term><term>Case-Control Studies</term><term>Cell Count (methods)</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Immunohistochemistry (methods)</term><term>Inflammation (etiology)</term><term>Inflammation (metabolism)</term><term>Inflammation (pathology)</term><term>Intercellular Adhesion Molecule-1 (physiology)</term><term>Leukocytes (pathology)</term><term>Lymphocyte Function-Associated Antigen-1 (metabolism)</term><term>MPTP Poisoning (chemically induced)</term><term>MPTP Poisoning (metabolism)</term><term>Macaca mulatta</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (complications)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (pathology)</term><term>Postmortem Changes</term><term>Substantia Nigra (cytology)</term><term>Substantia Nigra (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Lymphocyte Function-Associated Antigen-1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Intercellular Adhesion Molecule-1</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>MPTP Poisoning</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Inflammation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Astrocytes</term><term>Inflammation</term><term>MPTP Poisoning</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Cell Count</term><term>Immunohistochemistry</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Inflammation</term><term>Leukocytes</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Case-Control Studies</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Macaca mulatta</term><term>Male</term><term>Middle Aged</term><term>Postmortem Changes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">It has been established that neuroinflammation is present in the substantia nigra (SN) of Parkinson disease (PD) cases but the factors responsible are as yet unknown. One contributing protein may be the intercellular adhesion molecule-1 (ICAM-1, CD54). ICAM-1 with its counter receptor, the lymphocyte function-associated antigen 1 (LFA-1) is known to play a key role in inflammatory processes and in T-cell mediated host defense mechanisms. We detected large numbers of ICAM-1-positive reactive astrocytes in the SN of a series of 14 patients with neuropathologically confirmed PD, including 3 of familial origin, compared with 11 age-matched controls. In PD SN, these ICAM-1-positive reactive astrocytes were particularly concentrated around many residual neurons in areas of heavy neuronal loss and extracellular melanin accumulation. LFA-1-positive reactive microglia gathered in areas of intense ICAM-1 expression, and LFA-1-positive leukocytes were identified infiltrating the tissue. Double immunostaining for ICAM-1 and LFA-1 revealed aggregates of reactive microglia embedded in areas of diffuse ICAM-1. Leukocyte counts were 5 fold higher in PD SN compared to controls (P < 0.001). Similar over-expression of ICAM-1 was found in monkeys that had been exposed to MPTP from 5.5 to 14 years previously compared with control monkeys. The presence of ICAM-1-positive reactive astrocytes in Parkinson disease and MPTP-treated monkeys is indicative of a sustained inflammatory process and suggests that antiinflammatory agents may have a place in PD therapy.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Doudet, D D" sort="Doudet, D D" uniqKey="Doudet D" first="D D" last="Doudet">D D Doudet</name><name sortKey="Mcgeer, E G" sort="Mcgeer, E G" uniqKey="Mcgeer E" first="E G" last="Mcgeer">E G Mcgeer</name><name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P L" last="Mcgeer">P L Mcgeer</name><name sortKey="Schwab, C" sort="Schwab, C" uniqKey="Schwab C" first="C" last="Schwab">C. Schwab</name><name sortKey="Yu, S" sort="Yu, S" uniqKey="Yu S" first="S" last="Yu">S. Yu</name></noCountry><country name="Canada"><noRegion><name sortKey="Miklossy, J" sort="Miklossy, J" uniqKey="Miklossy J" first="J" last="Miklossy">J. Miklossy</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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