Soluble and cell-associated forms of the adhesion molecule LFA-3 (CD58) are differentially regulated by inflammatory cytokines.
The adhesion molecule lymphocyte function-associated antigen 3 (LFA-3) (CD58) is an important regulator of immune cell function which occurs as both surface-associated and 'soluble' forms. This study has investigated the inter-relationship and the effects of cytokines on the expression of LFA-3 isoforms. The surface antigen was found to be relatively unaffected by cytokines, but the release of soluble LFA-3 (sLFA-3) was highly responsive to interleukin 1beta (IL-1beta), interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha). This modulation was cell-specific, particularly with regard to IFN-gamma, which up-regulated sLFA-3 release by A431 cells but down-regulated the release of the soluble form from HEp2 and HepG2 cells. We further demonstrated that LFA-3 is also present in a cytoplasmic 'pool' in each of the cells and, moreover, that cleavage of LFA-3 from the cell surface by phospholipase C resulted in an increase in the levels of the intracellular LFA-3 and replacement of the membrane-associated antigen. These observations suggest that the expression of the surface, soluble and intracellular forms of LFA-3 may be linked by regulatory mechanisms which are likely to exert an important influence on inflammatory interactions.
Kirby
A C
AC
Department of Oral Medicine, Eastman Dental Institute for Oral Health Care Sciences, University College London, UK.
Cahen
P
P
Porter
S R
SR
Olsen
I
I
D018968:CD58 Antigens / Q000276:immunology* / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D019169:Jurkat Cells; D007822:Laryngeal Neoplasms; D008113:Liver Neoplasms; D008175:Lung Neoplasms; D010740:Phospholipases / Q000494:pharmacology; D012995:Solubility; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D018968:CD58 Antigens; D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D010740:Phospholipases