Expression of Cystatin C in Human Histiocytic Lymphoma, U-937, Cells.

Abstract

The established human histiocytic lymphoma U-937 cell line is of monocytic origin. U-937 cells can be induced by tumor promoters, Vitamin D3 and retinoic acid to differentiate into macrophage-like cells. U-937 cells express the gene for the cysteine proteinase inhibitor cystatin C. This was established by Northern blot hybridizations, reverse transcriptase-polymerase chain reaction and Western blots of partially purified cystatins from extracts of U-937 cells. Induction of macrophage-like differentiation by the tumor promoters phorbol-12-myristate-13-acetate or 12-O-tetradecanoylphorbol-13-acetate, or with Vitamin D3, or retinoic acid reduced the steady-state level of cystatin C mRNA in U-937 cells, suggesting that the expression of the cystatin C gene varies with the differentiation state. U-937 cells secrete cystatin C. This secretion was not affected significantly by the calcium ionophore A23187, PMA, or dibutyryl-adenosine 3′: 5′-cyclic monophosphate. Since macrophages play pivotal roles in immune and inflammatory reactions involving intra- and extra-cellular proteolysis, cystatin C produced and secreted by these cells probably has a modulatory function on the action of cysteine proteinases produced or released locally.