Mesangial cell accessory functions: mediation by intercellular adhesion molecule-1.
Mesangial cell (MC) proliferation is an early pathologic alteration characteristic of many forms of immune mediated glomerulonephritis. The intracapillary position, contractile capacity, and production of cytokines and other inflammatory molecules place MC in a pivotal position to initiate, mediate, and direct glomerular damage. We as well as others have noted increased levels of cytokines including IFN gamma, TNF, and IL-1 and the cell surface MHC class II and ICAM-1 molecules in the kidneys of mice with lupus nephritis. MHC class II and ICAM-1 molecules are central to the interaction of T cells with antigen presenting cells (APC). Since cytokines can increase both MHC class II and ICAM-1 molecules, we investigated whether mesangial cells could function as APC or accessory cells after cytokine stimulation. For these studies we established a permanent MC line through transformation with origin-deficient SV40 DNA. Surface expression of ICAM-1 was similar in untransformed MC as well as SV40 transformed MC from normal mice and in untransformed cells from mice with lupus nephritis. Basal expression of ICAM-1 was upregulated rapidly by IFN gamma, TNF, and IL-1. MHC class II expression could not be induced with TNF or IL-1 alone but required prolonged stimulation with IFN gamma. MC adhered and presented antigen to an antigen specific IaK restricted T cell hybridoma. Anti-ICAM-1 mAb decreased adhesion and antigen presentation of cytokine stimulated MC. By comparison, MHC class II mAb abrogated antigen presentation by MC bearing MHC class II but did not block adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Brennan
D C
DC
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital Boston, Massachusetts.
Jevnikar
A M
AM
Takei
F
F
Reubin-Kelley
V E
VE
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005920:Glomerular Mesangium / Q000166:cytology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1; D008181:Lupus Nephritis / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1