Imatinib therapy reduces radiation-induced pulmonary mast cell influx and delays lung disease in the mouse

Thomas, David M.; Fox, Jessica K.; Haston, Christina K.

doi:10.3109/09553001003674863

Cited by 31 publications

(39 citation statements)

References 41 publications

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“…Our survey on mitigation studies also shows that nearly all are confined to only one mouse strain. Only two reports have included strain comparison (among KK, AKR, and C3H mice) and show that the extension of MSTs upon treatment with imatinib mesylate 121 or the CXCR antagonist G3IP 122 can vary 2-to 3-fold among the different strains.…”

Section: Implications For Selecting the Best Models In The Pre-clinicmentioning

confidence: 99%

A survey of changing trends in modelling radiation lung injury in mice: bringing out the good, the bad, and the uncertain

Dabjan

Buck

Jackson

et al. 2016

Laboratory Investigation

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Within this millennium there has been resurgence in funding and research dealing with animal models of radiationinduced lung injury to identify and establish predictive biomarkers and effective mitigating agents that are applicable to humans. Most have been performed on mice but there needs to be assurance that the emphasis on such models is not misplaced. We therefore considered it timely to perform a comprehensive appraisal of the literature dealing with radiation lung injury of mice and to critically evaluate the validity and clinical relevance of the research. A total of 357 research papers covering the period of 1970-2015 were extensively reviewed. Whole thorax irradiation (WTI) has become the most common treatment for studying lung injury in mice and distinct trends were seen with regard to the murine strain, radiation dose, intended pathology investigated, length of study, and assays. Recently, the C57BL/6 strain has been increasingly used in the majority of these studies with the notion that they are susceptible to pulmonary fibrosis. Nonetheless, many of these investigations depend on animal survival as the primary end point and neglect the importance of radiation pneumonitis and the anomaly of lethal pleural effusions. A relatively large variation in survival times of C5BL/6 mice is also seen among different institutions pointing to the need for standardization of radiation treatments and environmental conditions. An analysis of mitigating drug treatments is complicated by the fact that the majority of studies are limited to the C57BL/6 strain with a premature termination of the experiments and do not establish whether the treatment actually prevents or simply delays the progression of radiation injury. This survey of the literature has pointed to several improvements that need to be considered in establishing a reliable preclinical murine model of radiation lung injury. The lethality end point should also be used cautiously and with greater emphasis on other assays such as non-invasive lung functional and imaging monitoring in order to quantify specific pulmonary injury that can be better extrapolated to radiation toxicity encountered in our own species.Laboratory Investigation (2016) 96, 936-949;

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Section: Implications For Selecting the Best Models In The Pre-clinicmentioning

confidence: 99%

A survey of changing trends in modelling radiation lung injury in mice: bringing out the good, the bad, and the uncertain

Dabjan

Buck

Jackson

et al. 2016

Laboratory Investigation

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“…Lung damage was induced by whole-thorax irradiation (18 Gy; dose rate 0.6 Gy/min) using a Gammacell 137 Cs unit as described previously (5,9,(19)(20)(21)(22). The rest of the body was shielded with 3 cm of lead to reduce the beam strength to 3% in this area.…”

Section: Radiation Treatmentmentioning

confidence: 99%

“…G31P treatment has also been shown to block acute neutrophil infiltration to the lungs of endotoxemic guinea pigs (16) and piglets (17) and to reduce bronchoalveolar lavage neutrophilia in mice exposed intranasally to benzo(a)-pyrene (18). To assess the effect of the antagonist on both alveolitis and fibrosis, we examined the responses of AKR/J and KK/HIJ mice, which develop these phenotypes, respectively, after whole-thorax irradiation (19).…”

Section: Introductionmentioning

confidence: 99%

Combined CXCR1/CXCR2 Antagonism Decreases Radiation-Induced Alveolitis in the Mouse

2011

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The mechanisms leading to the radiation-induced lung responses of alveolitis and fibrosis are largely unknown. Herein we investigated whether CXC receptor 1 and 2 antagonism with CXCL8((3-72))K11R/G31P (G31P), a protein that reduces neutrophil chemotaxis in acute inflammatory response models, decreases the lung response to radiation. Mice of the AKR/J (alveolitis/pneumonitis responding) and KK/HIJ (fibrosis) strains received 18 Gy whole-thorax irradiation and a subset of these mice were treated with G31P (500 µg/kg) three times per week from the day of irradiation until euthanasia due to respiratory distress symptoms or 20 weeks after radiation treatment. Irradiated mice of both strains receiving G31P survived longer than mice receiving radiation alone. Radiation- and G31P-treated AKR/J mice surviving to the end of the experiment developed significantly less alveolitis, as measured histologically, than mice receiving radiation alone, but this difference was not evident in KK/HIJ mice. Using immunohistochemistry, G31P treatment was shown to increase the numbers of Gr-1-positive cells (neutrophils) in the lungs of unirradiated mice relative to control mice injected with saline, but the antagonist did not alter the numbers of Gr-1-positive cells in the lungs of radiation-treated mice. We conclude that G31P treatment reduces radiation-induced alveolitis but not fibrosis in mice.

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“…At the age of 8-10 weeks, mice were exposed to a single dose of 18 Gy to the thorax using a Gamma Cell Cesium-137 source as previously described (22,26). Mice were weighed weekly beginning 8 weeks after irradiation.…”

Section: Thoracic Irradiation and Experimental Groupsmentioning

confidence: 99%

“…Mice were euthanized when they showed signs of distress (ruffled fur, accelerated breathing, hunched posture, weight loss .15% of body weight). For these studies, groups of C57BL/6J and Ja18 -/-mice were euthanized not only when they showed signs of distress but also at specific time points (16,20,26 and 35 weeks) postirradiation. Control mice were not irradiated and were euthanized at matching time points.…”

Section: Thoracic Irradiation and Experimental Groupsmentioning

confidence: 99%

NKT Deficient Mice are not Spared Lung Disease after Exposure to Thoracic Radiotherapy

2014

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Imatinib therapy reduces radiation-induced pulmonary mast cell influx and delays lung disease in the mouse

Abstract: We conclude that imatinib treatment reduces radiation-induced mast cell influx into the lungs and delays the alveolitis or fibrosis response of mice.

Cited by 31 publications

References 41 publications

A survey of changing trends in modelling radiation lung injury in mice: bringing out the good, the bad, and the uncertain

A survey of changing trends in modelling radiation lung injury in mice: bringing out the good, the bad, and the uncertain

Combined CXCR1/CXCR2 Antagonism Decreases Radiation-Induced Alveolitis in the Mouse

NKT Deficient Mice are not Spared Lung Disease after Exposure to Thoracic Radiotherapy

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