Granulocyte Macrophage Colony–Stimulating Factor–Driven Respiratory Mucosal Sensitization Induces Th2 Differentiation and Function Independently of Interleukin-4

2002 ◽  
Vol 27 (4) ◽  
pp. 428-435 ◽  
Author(s):  
Stacey A. Ritz ◽  
Meghan J. Cundall ◽  
Beata U. Gajewska ◽  
David Alvarez ◽  
José-Carlos Gutierrez-Ramos ◽  
...  
Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 2869-2879 ◽  
Author(s):  
Saroj K. Basak ◽  
Airi Harui ◽  
Marina Stolina ◽  
Sherven Sharma ◽  
Kohnosuke Mitani ◽  
...  

Abstract Dendritic cells (DCs) are rare antigen-presenting cells that play a central role in stimulating immune responses. The combination of recombinant granulocyte macrophage–colony-stimulating factor (rGM-CSF) and recombinant interleukin-4 (rIL-4) provides an important stimulus for generating DCs from murine bone marrow precursors in vitro. Using miniature osmotic pumps, we now demonstrate that continuous infusion of these cytokines for 7 days had a similar effect in vivo, increasing the number and function of splenic DCs. Administration of rGM-CSF/rIL-4 (10 μg/d each) increased the concentration of CD11+ DCs by 2.7-fold and the absolute number of splenic DCs by an average of 5.7-fold. DC number also increased in peripheral blood and lymph nodes. The resultant DCs exhibited a different phenotype and function than those in control mice or mice treated with rGM-CSF alone. rGM-CSF/IL-4 increased both the myeloid (CD11c+/CD11b+) and the lymphoid (CD11c+/CD8α+) subpopulations, whereas rGM-CSF increased only myeloid DCs. DCs were highly concentrated in the T-cell areas of white pulp after rGM-CSF/IL-4 administration, whereas they were diffusely distributed throughout white pulp, marginal zones, and red pulp in mice treated with rGM-CSF alone. rGM-CSF/rIL-4 also significantly increased the expression of major histocompatibility complex (MHC) class I and MHC class II on CD11c+ cells and increased their capacity to take up antigens by macropinocytosis and receptor-mediated endocytosis. Splenic DCs generated in response to rGM-CSF/rIL-4 were functionally immature in terms of allostimulatory activity, but this activity increased after short-term in vitro culture. Systemic treatment with rGM-CSF/rIL-4 enhanced the response to an adenoviral-based vaccine and led to antigen-specific retardation in the growth of established tumor. We conclude that systemic therapy with the combination of rGM-CSF/rIL-4 provides a new approach for generating DCs in vivo.


1996 ◽  
Vol 270 (4) ◽  
pp. L650-L658 ◽  
Author(s):  
M. Ikegami ◽  
T. Ueda ◽  
W. Hull ◽  
J. A. Whitsett ◽  
R. C. Mulligan ◽  
...  

Mice made granulocyte macrophage-colony stimulating factor (GM-CSF)-deficient by homologous recombination maintain normal steady-state hematopoiesis but have an alveolar accumulation of surfactant lipids and protein that is similar to pulmonary alveolar proteinosis in humans. We asked how GM-CSF deficiency alters surfactant metabolism and function in mice. Alveolar and lung tissue saturated phosphatidylcholine (Sat PC) were increased six- to eightfold in 7- to 9-wk-old GM-CSF-deficient mice relative to controls. Incorporation of radiolabeled palmitate and choline into Sat PC was higher in GM-CSF deficient mice than control mice, and no loss of labeled Sat PC occurred from the lungs of GM-CSF-deficient mice. Secretion of radiolabeled Sat PC to the alveolus was similar in GM-CSF-deficient and control mice. Labeled Sat PC and surfactant protein A (SP-A) given by tracheal instillation were cleared rapidly in control mice, but there was no measurable loss from the lungs of GM-CSF-deficient mice. The function of the surfactant from GM-CSF-deficient mice was normal when tested in preterm surfactant-deficient rabbits. GM-CSF deficiency results in a catabolic defect for Sat PC and SP-A.


2003 ◽  
Vol 60 (5) ◽  
pp. 531-538 ◽  
Author(s):  
Miodrag Colic ◽  
Dusan Jandric ◽  
Zorica Stojic-Vukanic ◽  
Jelena Antic-Stankovic ◽  
Petar Popovic ◽  
...  

Several laboratories have developed culture systems that allow the generation of large numbers of human dendritic cells (DC) from monocytes using granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukin-4 (IL-4). In this work we provided evidence that GM-CSF (100 ng/ml) in combination with a low concentration of IL-4 (5 ng/ml) was efficient in the generation of immature, non-adherent, monocyte-derived DC as the same concentration of GM-CSF, and ten times higher concentration of IL-4 (50 ng/ml). This conclusion was based on the similar phenotype profile of DC such as the expression of CD1a, CD80, CD86, and HLA-DR, down-regulation of CD14, and the absence of CD83, as well as on their similar allostimulatory activity for T cells. A higher number of cells remained adherent in cultures with lower concentrations of IL-4 than in cultures with higher concentrations of the cytokine. However, most of these adherent cells down-regulated CD14 and stimulated the proliferation of alloreactive T cells. In contrast adherent cells cultivated with GM-CSF alone were predominantly macrophages as judged by the expression of CD14 and the inefficiency to stimulate alloreactive T cells. DC generated in the presence of lower concentrations of IL-4 had higher proapoptotic potential for the Jurkat cell line than DC differentiated with higher concentrations of IL-4, suggesting their stronger cytotoxic, anti-tumor effect.


2020 ◽  
Vol 105 ◽  
pp. 103586 ◽  
Author(s):  
Zhiguang Wu ◽  
Rakhi Harne ◽  
Cosmin Chintoan-Uta ◽  
Tuan-Jun Hu ◽  
Robert Wallace ◽  
...  

1994 ◽  
Vol 15 (5) ◽  
pp. 1017-1029 ◽  
Author(s):  
Fredika M. Robertson ◽  
Gautam N. Bijur ◽  
Andrew S. Oberyszyn ◽  
Arthur E. Pellegrini ◽  
Laszlo G. Boros ◽  
...  

1996 ◽  
Vol 60 (5) ◽  
pp. 644-650 ◽  
Author(s):  
Persio Dello Sbarba ◽  
Elisabetta Rovida ◽  
Barbara Caciagli ◽  
Lucia Nencioni ◽  
Danilo Labardi ◽  
...  

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