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-specific regulation and not redundancy of TNF production, we investigated its production by alveolar macrophages (AM) and peritoneal mast cells (PMC). Cell lysates of freshly isolated AM and PMC contained 9 +/- 3 pg and 57 +/- 17 pg of TNF/10(6) cells, respectively. Furthermore, unstimulated PMC expressed 4 x 10(3)-fold more attomols of TNF mRNA/microg 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 cytotoxic activity than AM (sevenfold), suggesting that PMC express more membrane TNF than AM. Although AM and PMC contain different amounts of TNF, antigen stimulation caused a similar release of TNF from sensitized rats. Interferon (IFN)-gamma, respectively, stimulated and inhibited AM and PMC TNF-dependent cytotoxicity whereas lipopolysaccharide (LPS) significantly stimulated TNF-dependent cytotoxicity in both cell types. However, TNF released (AM 400-fold and PMC threefold) and TNF mRNA expression, as measured by competitive 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 cells.
Déry
R E
RE
Department of Medicine, Pulmonary Research Group, University of Alberta, Edmonton, Canada.
Lin
T J
TJ
Befus
A D
AD
Milne
C D
CD
Moqbel
R
R
Ménard
G
G
Bissonnette
E Y
EY
D000818:Animals; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D010537:Peritoneum / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma