Distinct functions of interferon‐γ for chemokine expression in models of acute lung inflammation

Abstract

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.

Neutrophil Depletion Causes a Fatal Defect in Murine Pulmonary Staphylococcus aureus clearance

“…While no studies correlating S. aureus pneumonia and MCP-1 have been performed in mice, this has been examined in a number of related models. Pulmonary MCP-1 is increased following administration of the superantigen staphylococcal enterotoxin B; however, this is unrelated to IFN-γ, since MCP-1 levels are similar in control and IFN-γ-knockout mice (34). Pseudomonas aeruginosa pneumonia increases MCP-1 levels, associated with increased numbers of alveolar macrophages.…”

NKT Cell Activation Mediates Neutrophil IFN-γ Production and Renal Ischemia-Reperfusion Injury

“…At an early time point of renal IRI, we demonstrated an increase in the influx of CD4 ϩ T cells and NKT cells. Chemokines mediate leukocyte migration into the injured kidney and IFN-␥ modulates chemokine production, including IFN-␥-inducing protein 10 (IP-10), monokine-induced by IFN-␥, and IFN-␥-inducible T cell chemoattractant production, which bind to CXCR3 to mediate T cell migration (25) (25)(26)(27)(28)(29)(30). Our previous study showed that renal IRI up-regulated IP-10 and MIP␣, MIP1␤, MIP2, which are thought to mediate T cell and neutrophil migration (31,32).…”

Chemokine Expression Dynamics in Mycobacterial (Type-1) and Schistosomal (Type-2) Antigen-Elicited Pulmonary Granuloma Formation

“…Furthermore, some CKs such as LIX and MIP-2 were induced independently of TNF-␣ as was previously reported in TNF receptor knockout mice stimulated with superantigens. 74 It should be noted that because of the great effort required to monitor numerous CKs in multiple samples we focused analysis on the rapid recruitment period, day 2. Further studies will be needed to determine whether later stage CKs are influenced by cytokine depletions.…”