Treatment of an Infected Murine Macrophage Cell Line (J774A.1) with Interferon-γ but Not Tumor Necrosis Factor-α 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-α (rTNF-α) or recombinant murine interferon-γ (rIFN-γ) 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-γ 1 day before the addition of the bacteria. The addition of IFN-γ with M. intracellulare simultaneously, however, did not affect the expression of the adhesion molecules as compared with the IFN-γ alone. Our results indicated no change in the level of LFA-1 on J774A.1 following exposure with TNF-α. We observed that preexposure with 10–10⁴ IU/ml of TNF-α can significantly decrease the number of ingested M. intracellulare. Simultaneous addition of 10³ and 10⁴ IU/ml of TNF-α, however, did not have any mycobactericidal effect. This indicates that the TNF-α-induced killing by J774A.1 cells was relatively selective, depending on the concentration and the time of presence of TNF-α. The data may suggest that the uptake of M. intracellulare is carried out via other adhesion receptors when M. intracellulare and IFN-α are present simultaneously and that in the presence of TNF-a 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-1β or MAC-1, a finding comparable with that of the J774A.1 cells.