Expression of chemokine receptors CCR1 and CCR5 reflects differential activation of mononuclear phagocytes in pattern II and pattern III multiple sclerosis lesions.
Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. A recent study identified 4 patterns of demyelination in active MS lesions. The characteristics of pattern II lesions suggested a primary inflammatory mechanism of myelin injury, while pattern III lesions showed features consistent with dying-back oligodendrogliopathy. The recruitment, differentiation, and activation of mononuclear phagocytes are dependent on the expression of chemokine receptors. Using immunohistochemistry we quantified cellular expression of CCR1 and CCR5 in pattern II (n = 21) and pattern III (n = 17) lesion areas of differing demyelinating activity. Infiltrating monocytes in both lesion patterns co-expressed CCR1 and CCR5, suggesting conserved mechanisms of monocyte recruitment into the CNS. In pattern II lesions, the number of cells expressing CCR1 significantly decreased while CCR5 increased in late active compared with early active demyelinating regions. In striking contrast, numbers of cells expressing CCR1 and CCR5 were equal in all regions of pattern III lesions. As hypoxia-like mechanisms may play a role in pattern III lesions, we extended these studies to white matter infarcts (n = 7) in which the expression of CCR1 better resembled pattern III than pattern II lesions. As judged by mononuclear phagocyte chemokine receptor expression, there appear to be distinct tissue environments in pattern II and III MS lesions.
Mahad
Don J
DJ
Department of Neurosciences, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Trebst
Corinna
C
Kivisäkk
Pia
P
Staugaitis
Susan M
SM
Tucky
Barbara
B
Wei
Tao
T
Lucchinetti
Claudia F
CF
Lassmann
Hans
H
Ransohoff
Richard M
RM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D015415:Biomarkers; D018925:Chemokines / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D009186:Myelin Sheath / Q000276:immunology / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000276:immunology / Q000473:pathology; D009836:Oligodendroglia / Q000276:immunology / Q000473:pathology; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000276:immunology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018925:Chemokines; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; C515300:CCR1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule