scholarly journals Early Cytokine and Chemokine Gene Expression duringPseudomonas aeruginosa Corneal Infection in Mice

1998 ◽  
Vol 66 (1) ◽  
pp. 376-379 ◽  
Author(s):  
Karen A. Kernacki ◽  
Dennis J. Goebel ◽  
Michael S. Poosch ◽  
Linda D. Hazlett
Keyword(s):  
Transforming Growth Factor ◽  
Rnase Protection Assay ◽  
Colony Stimulating Factor ◽  
Necrosis Factor Alpha ◽  
Rnase Protection ◽  
Corneal Infection ◽  
Cytokines And Chemokines ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

ABSTRACT Using a multiprobe RNase protection assay, we examined cytokine and chemokine mRNAs that were expressed after corneal infection withPseudomonas aeruginosa in mice. Cytokines that were upregulated included interleukin-1α (IL-1α) and -1β, IL-1 receptor antagonist, IL-6, IL-11, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, lymphotoxin β, transforming growth factor β1, and tumor necrosis factor alpha. Chemokine transcripts that were upregulated included Eotaxin; gamma-interferon-inducible protein 10; monocyte chemoattractant protein 1; macrophage inflammatory proteins 1α, 1β, and 2; and RANTES. Peak expression of these cytokines and chemokines was observed between 1 and 3 days after infection. These responses returned to or approached baseline preinfection levels by 7 days after ocular challenge. Identification of the various cytokines and chemokines upregulated during corneal infection provides important information relevant to unraveling the pathogenesis induced by this bacterium and provides hope that specific molecules can be targeted for therapy.

scholarly journals Neutrophils activated by granulocyte-macrophage colony-stimulating factor express receptors for interleukin-3 which mediate class II expression

Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3938-3944 ◽  
Author(s):  
WB Smith ◽  
L Guida ◽  
Q Sun ◽  
EI Korpelainen ◽  
C van den Heuvel ◽  
...  
Keyword(s):  
Class Ii ◽  
Colony Stimulating Factor ◽  
Necrosis Factor Alpha ◽  
Rnase Protection ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Hla Dr ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Freshly isolated peripheral blood neutrophils, unlike monocytes and eosinophils, do not bind interleukin-3 (IL-3) or respond to IL-3). We show that neutrophils cultured for 24 hours in granulocyte-macrophage colony-stimulating factor (GM-CSF) express mRNA for the IL-3 receptor (R) alpha subunit, as shown by RNase protection assays, and IL-3R alpha chain protein, as shown by cytometric analysis using two different specific monoclonal antibodies. This effect was selective for GM-CSF, because granulocyte colony-stimulating factor, tumor necrosis factor- alpha, interferon-gamma, and IL-1 failed to induce the IL-3 receptor. Saturation binding curves with 125I-IL-3 and Scatchard transformation showed the presence of about 100 high-affinity and 4,000 low-affinity receptors. Because neutrophils have been shown to express human leukocyte antigen (HLA)-DR in response to GM-CSF, we examined the possibility that IL-3 could augment HLA-DR expression on GM-CSF-treated cells. We found that neutrophils incubated with 30 ng/mL IL-3 as well as 0.1 ng/mL GM-CSF expressed a mean of 2.1-fold higher levels of HLA- DR than with GM-CSF alone (P < .005), confirming the signaling competence of the newly expressed IL-3R. This increase was seen even at maximal concentrations of GM-CSF and IL-3 can have an additive effect on mature human cells. The augmentation of HLA-DR by IL-3 was specific because it could be inhibited by a blocking anti-IL-3R antibody. Expression of class II molecules by neutrophils under these conditions may have significance for antigen presentation. These results provide further evidence for the role of GM-CSF as an amplification factor in inflammation by inducing neutrophil responsiveness to IL-3 produced by T cells or mast cells.

scholarly journals Granulocyte-Macrophage Colony-Stimulating Factor-Deficient Mice Have Impaired Resistance to Blood-Stage Malaria

2001 ◽  
Vol 69 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Julie Riopel ◽  
MiFong Tam ◽  
Karkada Mohan ◽  
Michael W. Marino ◽  
Mary M. Stevenson
Keyword(s):  
Blood Stage ◽  
Colony Stimulating Factor ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony Stimulating Factor ◽  
Ifn Γ ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Blood Stage Malaria

ABSTRACT The contribution of granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting GM-CSF-deficient (knockout [KO]) mice with Plasmodium chabaudi AS. KO mice were more susceptible to infection than wild-type (WT) mice, as evidenced by higher peak parasitemia, recurrent recrudescent parasitemia, and high mortality. P. chabaudiAS-infected KO mice had impaired splenomegaly and lower leukocytosis but equivalent levels of anemia compared to infected WT mice. Both bone marrow and splenic erythropoiesis were normal in infected KO mice. However, granulocyte-macrophage colony formation was significantly decreased in these tissues of uninfected and infected KO mice, and the numbers of macrophages in the spleen and peritoneal cavity were significantly lower than in infected WT mice. Serum levels of gamma interferon (IFN-γ) were found to be significantly higher in uninfected KO mice, and the level of this cytokine was not increased during infection. In contrast, IFN-γ levels were significantly above normal levels in infected WT mice. During infection, tumor necrosis factor alpha (TNF-α) levels were significantly increased in KO mice and were significantly higher than TNF-α levels in infected WT mice. Our results indicate that GM-CSF contributes to resistance to P. chabaudi AS infection and that it is involved in the development of splenomegaly, leukocytosis, and granulocyte-macrophage hematopoiesis. GM-CSF may also regulate IFN-γ and TNF-α production and activity in response to infection. The abnormal responses seen in infected KO mice may be due to the lack of GM-CSF during development, to the lack of GM-CSF in the infected mature mice, or to both.

scholarly journals Vascular Smooth Muscle Cell–Derived Transforming Growth Factor-β Promotes Maturation of Activated, Neointima Lesion–Like Macrophages

2014 ◽  
Vol 34 (4) ◽  
pp. 877-886 ◽  
Author(s):  
Allison Ostriker ◽  
Henrick N. Horita ◽  
Joanna Poczobutt ◽  
Mary C.M. Weiser-Evans ◽  
Raphael A. Nemenoff
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Macrophage Activation ◽  
Transforming Growth Factor ◽  
Conditioned Media ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Objective— To define the contribution of vascular smooth muscle cell (SMC)–derived factors to macrophage phenotypic modulation in the setting of vascular injury. Approach and Results— By flow cytometry, macrophages (M4) were the predominant myeloid cell type recruited to wire-injured femoral arteries, in mouse, compared with neutrophils or eosinophils. Recruited macrophages from injured vessels exhibited a distinct expression profile relative to circulating mononuclear cells (peripheral blood monocytes; increased: interleukin-6, interleukin-10, interleukin-12b, CC chemokine receptor [CCR]3, CCR7, tumor necrosis factor-α, inducible nitric oxide synthase, arginase 1; decreased: interleukin-12a, matrix metalloproteinase [MMP]9). This phenotype was recapitulated in vitro by maturing rat bone marrow cells in the presence of macrophage-colony stimulating factor and 20% conditioned media from cultured rat SMC (sMφ) compared with maturation in macrophage-colony stimulating factor alone (M0). Recombinant transforming growth factor (TGF)-β1 recapitulated the effect of SMC conditioned media. Macrophage maturation studies performed in the presence of a pan-TGF-β neutralizing antibody, a TGF-β receptor inhibitor, or conditioned media from TGF-β–depleted SMCs confirmed that the SMC-derived factor responsible for macrophage activation was TGF-β. Finally, the effect of SMC-mediated macrophage activation on SMC biology was assessed. SMCs cocultured with sMφ exhibited increased rates of proliferation relative to SMCs cultured alone or with M0 macrophages. Conclusions— SMC-derived TGF-β modulates the phenotype of maturing macrophages in vitro, recapitulating the phenotype found in vascular lesions in vivo. SMC-modulated macrophages induce SMC activation to a greater extent than control macrophages.

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