ICAM-1-dependent fibroblast-lymphocyte adhesion: discordance between surface expression and function of ICAM-1.
We have previously reported that stimulation of human fibroblasts (FB) with interferon-gamma (IFN-gamma) leads to their increased adhesiveness for resting peripheral blood T lymphocytes. With the use of blocking monoclonal antibodies, we determined that intercellular adhesion molecule-1 (ICAM-1) and its T cell ligand, lymphocyte function-associated antigen-1 (LFA-1) are the major, if not only ligands involved in this system. Using an ELISA, we have confirmed earlier reported observations that IFN-gamma induces an increase of ICAM-1 expression on the surface of FB suggesting that this increase mediates lymphocyte adhesion. However, we show that treatment of FB with IL-1, while leading to comparable increases in ICAM-1 synthesis and expression, failed to induce increased adhesion. In contrast, treatment of fibroblasts with the phorbol ester, TPA, stimulated ICAM-1-dependent adhesion without an increase in ICAM-1 surface expression. This suggested that the detection of ICAM-1 by monoclonal antibody techniques may not always correlate with its functional capabilities. The contrasting effects of IFN-gamma and IL-1 on ICAM-1-dependent FB adhesion suggest that qualitative as well as quantitative alterations of the ICAM-1 molecule may regulate ligand interaction.
Piela
T H
TH
Division of Rheumatic Diseases, Veterans Administration Medical Center, Newington, Connecticut.
Korn
J H
JH
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1; D011233:Precipitin Tests; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma