Glycohistochemical characterization of vascular muscle cell destruction in CADASIL subjects by lectins, neoglycoconjugates and galectin-specific antibodies.
CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a type of small-artery stroke and vascular dementia-inducing pathology of the brain. In order to explain the molecular mechanisms behind the alterations to the blood vessels in CADASIL subjects, we scrutinized the expression of glycan and glycan-binding sites in the wall of vessels taken from five such subjects (vs. five control subjects matched for age and sex). Specimens were taken from the brain, heart, kidney, liver and lung. Although the main vessel lesions were observed in the tissues depending on the blood-brain barrier, alterations to systemic vessels were also observed despite the absence of any symptoms. The histochemical expression of a panel of 10 biotinylated neoglycoconjugates [Gal-beta(1-4)-D-Glc, Galbeta(1-3)GalNAc, alpha-D-GalNAc, beta-D-GalNAc, GalNAcalpha(1-3)-D-GalNAcalpha, GalNAcalpha(1-3)-D-GalNAcbeta, beta-D-Glc, alpha-D-Man, l-Fucose and D-Glcalpha(1-4)-D-Glc], eight plant lectins (PNA, MAA, SNA, DBA, WGA, ConA, GNA and UEA-1) and two antigalectin antibodies was monitored by means of semiquantitative and quantitative computer-assisted microscopy. The data show the altered histochemical binding of plant lectins, such as UEA-1 and ConA, in the vessel walls of CADASIL subjects. The present work, based upon staining by a panel of neoglycoconjugates, provides a biochemical characterization of the alteration of vessel walls in the brain compared to other organs including the heart, kidney, lung and liver in CADASIL as opposed to control subjects. These glycohistochemical results suggest a functional relevance of protein-carbohydrate interactions in this disease.
Brulin-Fardoux
P
P
Department of Neuropathology, CHRU Lille, Hôpital Roger Salengro, Lille, France.
Godfrain
C
C
Maurage
C-A
CA
De Reuck
J
J
Hauw
J-J
JJ
Kaltner
H
H
Bovin
N V
NV
Gabius
H-J
HJ
Ruchoux
M-M
MM
Kiss
R
R
Camby
I
I
D000328:Adult; D000918:Antibody Specificity; D015161:Dementia, Multi-Infarct / Q000276:immunology / Q000473:pathology*; D004187:Disaccharides / Q000276:immunology / Q000378:metabolism; D005260:Female; D037161:Galectins / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009005:Monosaccharides / Q000276:immunology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000473:pathology*
D004187:Disaccharides; D037161:Galectins; D006023:Glycoproteins; D037102:Lectins; D009005:Monosaccharides