Do Variations in Mast Cell Hyperplasia Account for Differences in Radiation-Induced Lung Injury among Different Mouse Strains, Rats and Nonhuman Primates?

Abstract

The role of mast cell infiltrates in the pathology of radiation damage to the lung has been a subject of continuing investigation over the past four decades. This has been accompanied by a number of proposals as to how mast cells and the secretory products thereof participate in the generation of acute inflammation (pneumonitis) and the chronic process of collagen deposition (fibrosis). An additional pathophysiology examines the possible connection between mast cell hyperplasia and pulmonary hypertension through the release of vasoactive mediators. The timing and magnitude of pneumonitis and fibrosis are known to vary tremendously among different genetic mouse strains and animal species. Therefore, we have systematically compared mast cell numbers in lung sections from nine mouse strains, two rat strains and nonhuman primates (NHP) after whole thorax irradiation (WTI) at doses ranging from 10–15 Gy and at the time of entering respiratory distress. Mice of the BALB/c strain had a dramatic increase in interstitial mast cell numbers, similar to WAG/Rij and August rats, while relatively low levels of mast cell infiltrate were observed in other mouse strains (CBA, C3H, B6, C57L, WHT and TO mice). Enumeration of mast cell number in five NHPs (rhesus macaque), exhibiting severe pneumonitis at 17 weeks after 10 Gy WTI, also indicated a low response shared by the majority of mouse strains. There appeared to be no relationship between the mast cell response and the strain-dependent susceptibility towards pneumonitis or fibrosis. Further investigations are required to explore the possible participation of mast cells in mediating specific vascular responses and whether a genetically diverse mast cell response occurs in humans.

Whole-thorax irradiation induces hypoxic respiratory failure, pleural effusions and cardiac remodeling

“…One of the most striking characteristics of effusions in this study is the presence of mast cells ( Table 3 B). These cells are increased in irradiated rat lungs [ 5 , 45 ]. Mast and other infiltrating cells release inflammatory mediators and cytokines in irradiated lungs that can alter vascular permeability and promote pulmonary hypertension.…”

“…BALB/c) show early pleural effusions with pneumonitis, as observed in our rats. This mouse strain also exhibits a strong mast cell infiltration in the lung, but the connection to pulmonary hypertension and cardiac injury remains to be explored [ 45 ]. Effusions were observed after whole-thoracic irradiation of non-human primates, with a frequency as high as 75% at 12 Gy [ 46 ].…”

Les mastocytes, stakhanovistes de l’immunité

“…Il a reçu l'accord de la Food and drug administration (FDA), aux États-Unis, pour traiter des mastocytoses systémiques chez l'adulte, à condition que le gène codant le récepteur c-Kit chez les patients ne soit pas muté [30]. Une étude, publiée en 2013, n'a pas mis en évidence de relation entre hyperplasie mastocytaire et susceptibilités au développement de l'inflammation et de la fibrose radique pulmonaire chez plusieurs souches de souris, de rats et chez le primate non humain, exposés à des doses de radiothérapie comprises entre 10 et 16 Gy sur la totalité du thorax [31]. Pourtant, une étude récente réalisée chez le rat démontre qu'après application d'une dose plus importante au thorax (18 Gy), l'administration préventive d'hespéridine, un flavonoïde que l'on retrouve dans les fruits et les légumes, en particulier l'orange, réduisait les dommages pulmonaires radio-induits [32].…”