Renal allograft rejection: induction and function of adhesion molecules on cultured epithelial cells.
The interaction of graft-infiltrating immune cells with donor parenchymal cells is an important early event in allograft rejection. This binding is stabilized by interaction of antigen-independent 'adhesion' molecules expressed on the two cell types. As the level of expression of these molecules can be altered during inflammation, a series of experiments was performed to examine the effects of the inflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on adhesion molecules expressed by cultured human renal tubular epithelial cells. These cells constitutively expressed ICAM-1 and LFA-3. Incubation with IFN-gamma increased expression of ICAM-1 but had no significant effect on expression of LFA-3 (P greater than 0.05). Incubation with TNF-alpha increased expression of both ICAM-1 and LFA-3; IFN-gamma synergized with TNF-alpha to further augment expression of these molecules. Peripheral blood lymphocytes (PBL) showed an enhanced binding to allogeneic renal epithelial cell monolayers which had been pretreated with IFN-gamma or TNF-alpha. MoAbs specific for ICAM-1 or its ligand LFA-1 inhibited adhesion of PBL to either IFN-gamma- or TNF-alpha-pretreated renal cells. By contrast, antibodies specific for LFA-3 or its ligand CD2 only significantly blocked PBL adhesion to renal cells which had been pretreated with TNF-alpha. Combination of antibodies specific for multiple components of the adhesion systems produced greater inhibition of adhesion than was produced by any single MoAb. These results suggest that the inflammatory cytokines IFN-gamma and TNF-alpha up-regulate expression of functional ICAM-1 and LFA-3 molecules which can augment the binding of potentially graft-damaging lymphoid cells to renal tubular epithelial cells.
Lin
Y
Y
Department of Surgery, Medical School, University of Newcastle upon Tyne, UK.
Kirby
J A
JA
Clark
K
K
Shenton
B K
BK
Forsythe
J L
JL
Proud
G
G
Taylor
R M
RM
D015703:Antigens, CD / Q000378:metabolism*; D018968:CD58 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells; D006084:Graft Rejection; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma