Activation of human macrophages. Comparison of other cytokines with interferon-gamma.

Nathan, Carl; Prendergast, Thomas J.; Wiebe, Michael E.; Stanley, E. Richard; Platzer, E.; Remold, Heinz G.; Welte, Karl; Rubin, Berish Y.; Murray, Henry W.

doi:10.1084/jem.160.2.600

Cited by 348 publications

(139 citation statements)

References 21 publications

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…This decrease in IFN-␥ production by alveolar macrophages isolated from STAT4 Ϫ/Ϫ mice is most likely due to decreased IL-12 responsiveness in the absence of STAT4. In addition, the broader reduction in cytokine production may be attributable to a loss of IFN-␥ priming of macrophages, which has been demonstrated previously in other macrophage populations (51)(52)(53)(54). Given the importance of alveolar macrophages to the elimination of bacterial pathogens from the lung, this defect in alveolar macrophage function is another potential mechanism underlying the impaired pulmonary clearance of Klebsiella in the absence of STAT4.…”

Section: Discussionmentioning

confidence: 61%

STAT4 Is a Critical Mediator of Early Innate Immune Responses against Pulmonary Klebsiella Infection

Deng

Zeng

Newstead

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Bacterial pneumonia is a leading cause of morbidity and mortality in the U.S. An effective innate immune response is critical for the clearance of bacteria from the lungs. IL-12, a key T1 cytokine in innate immunity, signals through STAT4. Thus, understanding how STAT4 mediates pulmonary immune responses against bacterial pathogens will have important implications for the development of rational immunotherapy targeted at augmenting innate immunity. We intratracheally administered Klebsiella pneumoniae to wild-type BALB/c and STAT4 knockout (STAT4−/−) mice. Compared with wild-type controls, STAT4−/− mice had decreased survival following intratracheal Klebsiella administration, which was associated with a higher lung and blood bacterial burden. STAT4−/− animals also displayed impaired pulmonary IFN-γ production and decreased levels of proinflammatory cytokines, including the ELR− CXC chemokines IFN-γ-inducible protein-10 and monokine induced by IFN-γ. Although total lung leukocyte populations were similar between STAT4−/− and wild-type animals following infection, alveolar macrophages isolated from infected STAT4−/− mice had decreased production of proinflammatory cytokines, including IFN-γ, compared with infected wild-type mice. The intrapulmonary overexpression of IFN-γ concomitant with the systemic administration of IFN-γ partially reversed the immune deficits observed in STAT4−/− mice, resulting in improved bacterial clearance from the blood. Collectively, these studies demonstrate that STAT4 is required for the generation of an effective innate host defense against bacterial pathogens of the lung.

show abstract

Section: Discussionmentioning

confidence: 61%

STAT4 Is a Critical Mediator of Early Innate Immune Responses against Pulmonary Klebsiella Infection

Deng

Zeng

Newstead

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…A variety of chemical and biological agents, including LPS and IFN-'y, activate macrophages, as assessed by morphologic criteria, secretion of plasminogen activator, phagocytosis of opsonized erythrocytes, suppression of 5'-nucleotidase activity, production of oxidative metabolites, and destruction of intracellular pathogens (13,14). However, with respect to the production of cachectin, macrophage activation induced by IFN-y differs from activation induced by LPS.…”

Section: Discussionmentioning

confidence: 99%

Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype.

Beutler¹,

Tkacenko²,

Milsark³

et al. 1986

The Journal of Experimental Medicine

228

View full text Add to dashboard Cite

IFN-gamma permits the endotoxin-induced production of cachectin by C3H/HeJ (endotoxin resistant) macrophages, apparently by facilitating endotoxin-induced cachectin biosynthesis at both transcriptional and posttranscriptional levels. IFN-gamma cannot induce cachectin biosynthesis by itself, nor does it markedly enhance cachectin production by endotoxin-induced peritoneal macrophages obtained from endotoxin-responsive mice. Elucidation of the precise mechanism through which IFN-gamma influences cachectin biosynthesis may permit a better understanding of the molecular events that follow endotoxin-induced activation of macrophages. Moreover, the permissive effect of IFN-gamma on cachectin biosynthesis might elicit enhanced endotoxin sensitivity in vivo.

show abstract

“…For example, IFN-␥ stimulates macrophage activation 25 and enhances Fc␥R-mediated phagocytosis by augmenting Fc␥R levels. 26 IFN-␥ also influences T H1 /T H2 cell proliferation and function, enhancing humoral antibody production.…”

Section: Introductionmentioning

confidence: 99%

GM-CSF, via PU.1, regulates alveolar macrophage FcγR-mediated phagocytosis and the IL-18/IFN-γ–mediated molecular connection between innate and adaptive immunity in the lung

Berclaz

Shibata

Whitsett

et al. 2002

Blood

120

101

View full text Add to dashboard Cite

Severely impaired pulmonary microbial clearance was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)–deficient mice. To determine mechanisms by which GM-CSF mediates lung host defense, FcγR-mediated phagocytosis (opsonophagocytosis) by alveolar macrophages (AMs) was assessed in GM-CSF–sufficient (GM+/+) and –deficient (GM−/−) mice and in GM−/− mice expressing GM-CSF only in the lungs from a surfactant protein C (SPC) promoter (SPC-GM+/+/GM−/−). Opsonophagocytosis by GM−/− AMs was severely impaired and was restored by pulmonary GM-CSF expression in vivo or by PU.1 expression in vitro. Defective opsonophagocytosis by GM−/− AMs was associated with decreased FcγR expression. Because interferon-γ (IFN-γ) augments macrophage FcγR levels, the role of GM-CSF/PU.1 in the regulation of AM FcγR expression by IFN-γ was assessed during adenoviral lung infection. Adenoviral infection stimulated IFN-γ production and augmented FcγR levels on AMs in GM-CSF–expressing but not GM−/− mice. However, IFN-γ exposure ex vivo stimulated FcγR expression on GM−/− AMs. Because interleukin-18 (IL-18) and IL-12 stimulate IFN-γ production during adenoviral infection, their role in GM-CSF/PU.1 regulation of IFN-γ–augmented FcγR expression on AMs was assessed. Adenoviral infection stimulated IL-18 and IL-12 production in GM-CSF–expressing mice, but both were markedly reduced or absent in GM−/−mice. IL-18 expression by GM−/− AMs was severely impaired and was restored by pulmonary GM-CSF expression in vivo or by PU.1 expression in vitro. Pulmonary administration of IL-18 in GM−/− mice stimulated IFN-γ production and restored FcγR expression on AMs. These results show that GM-CSF, via PU.1, regulates constitutive AM FcγR expression and opsonophagocytosis and is required for the IFN-γ–dependent regulation of AM FcγR expression, enabling AMs to release IL-18/IL-12 during lung infection.

show abstract

Activation of human macrophages. Comparison of other cytokines with interferon-gamma.

Cited by 348 publications

References 21 publications

STAT4 Is a Critical Mediator of Early Innate Immune Responses against Pulmonary Klebsiella Infection

STAT4 Is a Critical Mediator of Early Innate Immune Responses against Pulmonary Klebsiella Infection

Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype.

GM-CSF, via PU.1, regulates alveolar macrophage FcγR-mediated phagocytosis and the IL-18/IFN-γ–mediated molecular connection between innate and adaptive immunity in the lung

Contact Info

Product

Resources

About