Redundancy or cell-type-specific regulation? Tumour necrosis factor in alveolar macrophages and mast cells

Tumour necrosis factor (TNF) is an important inflammatory cytokine produced by several cell types. To test the hypothesis that there is cell-type-spec ific regulation and not redundancy of TNF production, we investigated its p roduction by alveolar macrophages (AM) and peritoneal mast cells (PMC). Cel l lysates of freshly isolated AM and PMC contained 9 +/- 3 pg and 57 +/- 17 pg of TNF/10(6) cells, respectively. Furthermore, unstimulated PMC express ed 4 x 10(3)-fold more attomols of TNF mRNA/mu g total RNA compared with AM . These data may explain in part the greater TNF-dependent cytotoxicity of PMC. Furthermore, fixed PMC showed significantly higher TNF-dependent cytot oxic activity than AM (sevenfold), suggesting that PMC express more membran e TNF than AM. Although AM and PMC contain different amounts of TNF, antige n stimulation caused a similar release of TNF from sensitized rats. Interfe ron (IFN)-gamma, respectively, stimulated and inhibited AM and PMC TNF-depe ndent cytotoxicity whereas lipopolysaccharide (LPS) significantly stimulate d TNF-dependent cytotoxicity in both cell types. However, TNF released (AM 400-fold and PMC threefold) and TNF mRNA expression, as measured by competi tive reverse transcription-polymerase chain reaction (AM 7 x 10(3)-fold and PMC twofold), were considerably greater in LPS-stimulated AM than PMC. Our data indicate that TNF is differentially expressed in these two cell types and that its production is dependent on the nature of the stimulus. These data provide vital basis in experimental approaches aimed at modulating the effect of TNF in airway disease conditions involving both AM and mast cell s.