A Single Intratracheal Dose of the Growth Factor Fms-Like Tyrosine Kinase Receptor-3 Ligand Induces a Rapid Differential Increase of Dendritic Cells and Lymphocyte Subsets in Lung Tissue and Bronchoalveolar Lavage, Resulting in an Increased Local Antibody Production

Pabst, Reinhard; Lührmann, Anke; Steinmetz, Ivo; Tschernig, Thomas

doi:10.4049/jimmunol.171.1.325

Cited by 22 publications

(18 citation statements)

References 34 publications

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“…In addition, these cells were mature as shown by up-regulated expression of MHC II and CD86, and were potent APCs (4, 32). These results from murine studies are similar to a study from Pabst et al (33), who reported that intratracheal instillation of Flt3L induces expansion of different DC subsets and up-regulated immune responses in the lungs of rats.…”

Section: Discussionsupporting

confidence: 80%

Flt3-Ligand, IL-4, GM-CSF, and Adherence-Mediated Isolation of Murine Lung Dendritic Cells: Assessment of Isolation Technique on Phenotype and Function

Swanson

Zheng

Heidler

et al. 2004

The Journal of Immunology

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Lung dendritic cells (DCs) are difficult to study due to their limited quantities and the complexities required for isolation. Although many procedures have been used to overcome this challenge, the effects of isolation techniques on lung DCs have not been reported. The current study shows that freshly isolated DCs (CD11c+) have limited ability to induce proliferation in allogeneic T cells, and are immature as indicated by low cell surface expression of costimulatory molecules compared with liver or splenic DCs. DCs isolated after overnight culture or from mice treated with Flt3L are phenotypically mature and potent stimulators of allogeneic T cells. DCs could not be propagated from lung mononuclear cells in response to IL-4 and GM-CSF. Contrary to data reported for nonpulmonary DCs, expression of CCR6 was decreased on mature lung DCs, and only a subset of mature DCs expressed higher levels of CCR7. Absence of CD8α expression indicates that freshly isolated DCs are myeloid-type, whereas mature DCs induced by overnight culture are both “lymphoid” (CD8α+) and “myeloid” (CD8α−). DCs from mice genetically deficient in CD8α expression were strong simulators of allogeneic T cells which was consistent with data showing that CD8α− DCs from CD8α-sufficient mice are better APCs compared with CD8α+ DCs from the same mice. These data show that freshly isolated lung DCs are phenotypically and functionally distinct, and that the isolation technique alters the biology of these cells. Therefore, lung DC phenotype and function must be interpreted relative to the technique used for isolation.

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Section: Discussionsupporting

confidence: 80%

Flt3-Ligand, IL-4, GM-CSF, and Adherence-Mediated Isolation of Murine Lung Dendritic Cells: Assessment of Isolation Technique on Phenotype and Function

Swanson

Zheng

Heidler

et al. 2004

The Journal of Immunology

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“…For this i.t. instillation, a short combined isoflurane oxygen inhalation anesthesia was performed, and the rats were suspended in a hanging position by a rubber band fixed to the incisor teeth of the upper jaw (19). The trachea was intubated via the oral cavity, and the lungs were blown up with air before OVA instillation to check the correct position of the tube.…”

Section: Sensitization and Allergen Challenge In The Asthma Disease Mmentioning

confidence: 99%

“…In experiment 2, analysis of leukocyte subpopulations in blood, thymus, and spleens by FACS analysis was conducted as described above (19). In addition, immunohistochemistry was performed using mAbs characterizing NK cells (mAb 3.2.3), CD4…”

Section: Facs Analysis and Immunohistochemistry Of Leukocyte Subpopulmentioning

confidence: 99%

Postnatal Life Events Affect the Severity of Asthmatic Airway Inflammation in the Adult Rat

Kruschinski

Skripuletz

Bedoui

et al. 2008

The Journal of Immunology

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Genetic and hygienic factors influence susceptibility to asthma. In autoimmune and inflammatory diseases, additional effects of the psychosocial environment have been demonstrated that might also play a role in asthma. In this study, the impact of different early postnatal stressors on an OVA-induced model of asthma was tested in adulthood. Fischer 344 rats were subjected to either repeated handling stimulation (HA), maternal separation (MS), or were left undisturbed in their first 4 wk of life. Behavioral differences were characterized at the age of 4 mo. At 5 mo of age, immunological cellular and serologic changes were investigated and experimental asthma was induced. Results show significantly increased exploratory behavior and reduced anxiety in HA rats compared with MS and controls. Without further behavioral or immunological challenges, HA animals exhibited an increased ex vivo NK cell cytotoxicity but no other obvious immunological differences. After induction of asthma, in contrast, MS animals exhibited proinflammatory effects in leukocyte subset composition including increased eosinophil numbers, whereas levels of IgE and the allergy-specific cytokine IL-13 were reduced compared with HA. There was a most remarkable increase of adrenocorticotropin in HA animals, comparing pre- to postchallenge plasma levels. These data demonstrate for the first time that early postnatal stimulative or adverse experiences exert long-lasting changes of the “neuroendocrinoimmune” interface in adulthood, resulting in either protective or aggravating mechanisms in allergic airway disease. Thus, in addition to genetic and hygienic factors, nongenetically acquired individual differences contribute to the pathobiology of asthma.

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“…On the other hand, inoculation of tumor cells (22)(23)(24)(25) and DCs (26) expressing membrane bound or soluble FLT3L in mice models enhances anti-tumor immunity, while local administration of FLT3L plasmids (27,28) and soluble FLT3L (29) enhances local Th1 reaction. These facts indicate that FLT3L acts on peripheral blood cells, including DCs and NK cells.…”

Section: Introductionmentioning

confidence: 99%

Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and natural killer cells: Utilization for ovarian cancer treatment

Matsumura

Mandai²,

Hamanishi³

et al. 2008

Oncol Rep

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Abstract. Systemic administration of Fms-like tyrosine kinase 3 ligand (FLT3L) has been considered to be a major route of delivery for tumor immunotherapy because expression of its receptor, FLT3, was detected predominantly in hematopoetic progenitor cells. However, several studies indicate that FLT3L locally overexpressed in tumor or dendritic cells (DCs) also shows an anti-tumor effect. In the current study, we found that FLT3 expression is not present in monocytes but is instead induced in DCs through the differentiation process resulting from stimulation by GM-CSF and IL-4. Addition of FLT3L further augmented FLT3 induction and also increased CD40 expression in DCs, leading to enhanced induction of lymphoblastoid cell line-targeted cytotoxic Tlymphocyte response and CD107a mobilization in CD8 + T cells. Furthermore, FLT3L also induced FLT3 expression in peripheral blood NK cells that showed an enhanced response detected by CD107a mobilization. In a murine ovarian cancer model, locally expressed FLT3L showed anti-tumor effects. Collectively, the current study indicates that FLT3L has an immunostimulatory effect on peripheral blood cells and FLT3L targeted to mature peripheral blood cells may serve as a useful tool for cancer immunotherapy.

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A Single Intratracheal Dose of the Growth Factor Fms-Like Tyrosine Kinase Receptor-3 Ligand Induces a Rapid Differential Increase of Dendritic Cells and Lymphocyte Subsets in Lung Tissue and Bronchoalveolar Lavage, Resulting in an Increased Local Antibody Production

Cited by 22 publications

References 34 publications

Flt3-Ligand, IL-4, GM-CSF, and Adherence-Mediated Isolation of Murine Lung Dendritic Cells: Assessment of Isolation Technique on Phenotype and Function

Flt3-Ligand, IL-4, GM-CSF, and Adherence-Mediated Isolation of Murine Lung Dendritic Cells: Assessment of Isolation Technique on Phenotype and Function

Postnatal Life Events Affect the Severity of Asthmatic Airway Inflammation in the Adult Rat

Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and natural killer cells: Utilization for ovarian cancer treatment

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