Enhanced expression of chemotactic receptors in multiple sclerosis lesions.
We have previously shown that astrocytes and microglia express the receptors for C5a, interleukin-8 (IL-8) and N-formyl-Met-Leu-Phe (FMLP) in vitro. The expression and function of chemotactic receptors in the central nervous system (CNS) is, however, largely unexplored. In this study, we examined tissue sections from normal human brain and active, chronic active and chronic silent multiple sclerosis (MS) lesions for the expression of the receptors for C5a, IL-8 and FMLP by immunohistochemistry. In normal brain tissue, the expression of all three receptors was seen at low levels on astrocytes and microglia. In contrast, expression for all three receptors was markedly elevated on foamy macrophages in the acute and chronic active MS lesions. In addition, fibrous astrocytes stained intensely for the C5a receptor in the chronic active disease. Receptor expression in the chronic silent lesion was low and similar to that seen in normal brain, with staining confined to a few hypertrophic astrocytes and foamy macrophages. These are the first studies to demonstrate expression of these receptors in the CNS and elevated receptor expression in inflammatory MS lesions. The data suggest that these chemotactic receptors may play a role in inflammatory responses in MS and possibly in other CNS diseases.
Müller-Ladner
U
U
Department of Medicine, University of Alabama at Birmingham 35294, USA.
Jones
J L
JL
Wetsel
R A
RA
Gay
S
S
Raine
C S
CS
Barnum
S R
SR
D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D001923:Brain Chemistry / Q000502:physiology; D016022:Case-Control Studies; D002633:Chemotaxis / Q000502:physiology; D002908:Chronic Disease; D015936:Complement C5a; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000032:analysis*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000032:analysis*; D018123:Receptors, Interleukin / Q000032:analysis*; D023062:Receptors, Interleukin-8A; D018000:Receptors, Peptide / Q000032:analysis*; D013194:Staining and Labeling
D015703:Antigens, CD; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a