Mesangial cell accessory functions: Mediation by intercellular adhesion molecule-1

Daniel C. Brennan, Anthony M. Jevnikar, Fumio Takei, Vicki E. Reubin-Kelley

Research output: Contribution to journalArticlepeer-review

Abstract

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 IFNγ, 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 IFNγ, TNF, and IL-1. MHC class II expression could not be induced with TNF or IL-1 alone but required prolonged stimulation with IFNγ. MC adhered and presented antigen to an antigen specific Iak restricted T cell hyhridoma. 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. Thus, MC, by their unique glomerular location, contractile capacity, cytokine production, adherence, and antigen-presenting capability, are in a pivotal position to initiate and direct renal injury.

Original languageEnglish (US)
Pages (from-to)1039-1046
Number of pages8
JournalKidney international
Volume38
Issue number6
DOIs
StatePublished - Dec 1990
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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