Treatment of an infected murine macrophage cell line (J774A.1) with interferon-gamma but not tumor necrosis factor-alpha or live Mycobacterium intracellulare alone modulates the expression of adhesion molecules.

In the present study, we evaluated whether the activation of a murine macrophage cell line (J774.1A) by treatment with recombinant murine tumor necrosis factor-alpha (rTNF-alpha) or recombinant murine interferon-gamma (rIFN-gamma) before or simultaneous with infection with Mycobacterium intracellulare would affect their ability to express lymphocyte function-associated antigen-1 (LFA-1) and to restrict growth and kill the ingested M. intracellulare. The data showed that the effect of lipopolysaccharide (LPS) in increasing the level of LFA-1 was the same in the presence or absence of M. intracellulare. The inability of M. intracellulare to affect the level of expression of LFA-1 was irrespective of the M. intracellulare to J774A.1 ratio. A significant increase in the expression of LFA-1 was observed when J774A.1 cells were prestimulated with IFN-gamma 1 day before the addition of the bacteria. The addition of IFN-gamma with M. intracellulare simultaneously, however, did not affect the expression of the adhesion molecules as compared with the IFN-gamma alone. Our results indicated no change in the level of LFA-1 on J774A.1 following exposure with TNF-alpha. We observed that preexposure with 10-10(4) IU/ml of TNF-alpha can significantly decrease the number of ingested M. intracellulare. Simultaneous addition of 10(3) and 10(4) IU/ml of TNF-alpha, however, did not have any mycobactericidal effect. This indicates that the TNF-alpha-induced killing by J774A.1 cells was relatively selective, depending on the concentration and the time of presence of TNF-alpha. The data may suggest that the uptake of M. intracellulare is carried out via other adhesion receptors when M. intracellulare and IFN-alpha are present simultaneously and that in the presence of TNF-alpha other surface receptors are involved in the uptake of M. intracellulare. Flow cytometry analysis of the spleen cells removed at various times from M. intracellulare-infected mice also indicated no change in the level of LFA-1 beta or MAC-1, a finding comparable with that of the J774A.1 cells.