MUTZ-3, A MONOCYTIC MODEL CELL-LINE FOR INTERLEUKIN-4 AND LIPOPOLYSACCHARIDE STUDIES

The human monocytic cell lines MUTZ-3 and MONO-MAC-B express the lipop olysaccharide (LPS) receptor CD14. Paralleling the situation in periph eral blood monocytes (PBMo), recombinant human interleukin-4 (IL-4) do wn-regulated the expression of CD14 on the cell surface of MUTZ-3, but not that of MONO-MAC-6 cells. In addition, preincubation with IL-4 pr evented the LPS-induced up-regulation of IL-1 beta mRNA levels in MUTZ -3, but not in MONO-MAC-6 cells. We examined whether the differential responsiveness of the cell lines was due to the missing expression of the IL-4 receptor (IL-4R) alpha or gamma(c) chain in MONO-MAC-6 cells. Flow cytometric and immunoprecipitation analysis revealed expression of both IL-4R chains in both cell lines. In addition, short-term stimu lation with IL-4 induced tyrosine-phosphorylation of the gamma(c) chai n. As both cell lines also expressed signal transducer and activator o f transcription 6 (STAT 6), our data suggested that the differential r eaction patterns of MUTZ-3 and MONO-MAC-6 cells were not due to a gene rally defective IL-4R complex. Interestingly, long-term (48 hr) treatm ent with LPS rendered MONO-MAC-6 cells sensitive to IL-4. LPS up-regul ated expression of monocyte-specific esterase (MSE) mRNA as well as CD 14 protein in MONO-MAC-6 cells; both effects were inhibited by IL-4. T his stimulation was not paralleled by an increase of IL-4R mRNA or pro tein expression supporting the above hypothesis of a constitutively pr esent and active IL-4R. We discuss possible causes for the differentia l reaction patterns of MUTZ-3 and MONO-MAC-6 cells to IL-4.