Distinct functions of interferon-gamma for chemokine expression in models of acute lung inflammation.
Challenge of the immune system with bacterial superantigens or endotoxin induces the systemic release of cytokines followed by lethal septic shock. The lung is particularly susceptible to systemic toxin exposure resulting in acute leucocyte infiltration and vascular damage. In the present study, the functions of interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) for chemokine regulation during acute lung inflammation were examined. Following administration of the superantigen, staphylococcal enterotoxin B (SEB), lung mRNA levels of the chemokines cytokine-induced neutrophil chemo-attractant (KC), lipopolysaccharide-induced CXC chemokine (LIX), macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha and MIP-2 were increased to a similar extent both in controls and in mice deficient for the IFN-gamma or 55 000 MW TNF receptors. In contrast, interferon-inducible protein-10 (IP-10) and monokine induced by IFN-gamma (Mig) mRNA expression was markedly reduced in mice deficient for IFN-gamma or IFN-gamma receptor, but not in 55 000 MW TNF receptor knockout mice. In situ hybridization experiments demonstrated that IP-10 was highly expressed in lung interstitial macrophages of C57BL/6, but not of IFN-gamma receptor-deficient mice. In contrast to SEB administration, treatment with lipopolysaccharide resulted in a strong induction of IP-10 and Mig in IFN-gamma receptor-deficient mice. Together, these results establish a critical function of IFN-gamma for chemokine induction in acute lung inflammation that is dependent on the nature of the inflammatory stimulus.
Neumann
B
B
Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Emmanuilidis
K
K
Stadler
M
M
Holzmann
B
B
D000208:Acute Disease; D000818:Animals; D054357:Chemokine CXCL10; D018925:Chemokines / Q000032:analysis / Q000096:biosynthesis*; D019742:Chemokines, CC / Q000032:analysis / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology*; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000276:immunology*; D017471:Receptors, Interferon / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus; D018089:Superantigens / Q000494:pharmacology
D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D004768:Enterotoxins; D017471:Receptors, Interferon; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma