Exposure of human peripheral blood monocytes to bacterial products, phorbol esters, cyclic adenosine monophosphate (cAMP) and cAMP agonists stimulate the surface expression of a membrane activation antigen, the glycoprotein Mo3. Mo3 is recognized by two monoclonal antibodies Mo3e (IgM) and Mo3f (IgG). Surface expression of Mo3 is barely detectable on nonstimulated monocytes, but is expressed in high density on stimulated monocytes and monocytes found in inflammatory tissue. We have found increased expression of Mo3 on circulating monocytes from patients with chronic progressive multiple sclerosis (CPMS) and relapsing remitting MS (RRMS). We have not found increased surface Mo3 (sMo3) in any other disease control group tested. Preliminary studies indicate that Mo3 may be the urokinase plasminogen activator receptor and may have a role in migration inhibition factor (MIF) function. Thus, Mo3+ monocytes may be primed for migration from the blood into the tissue. That MS monocytes express increased sMo3 suggests that in vivo stimulation of monocytes is an ongoing process. We propose in this application to complete clinical correlations in aim #1; to examine whether MS Mo3+ monocytes express other phenotypic and functional correlates of activation in aim #2; to examine Mo3 gene expression using Mo3 cDNA in aim #3.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS029763-01A2
Application #
2267873
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1993-12-01
Project End
1996-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Wayne State University
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Balabanov, R; Beaumont, T; Dore-Duffy, P (1999) Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T-lymphocytes. J Neurosci Res 55:578-87
Balabanov, R; Dore-Duffy, P (1998) Role of the CNS microvascular pericyte in the blood-brain barrier. J Neurosci Res 53:637-44
Balabanov, R; Washington, R; Wagnerova, J et al. (1996) CNS microvascular pericytes express macrophage-like function, cell surface integrin alpha M, and macrophage marker ED-2. Microvasc Res 52:127-42