Temporal Sequence of Early Alterations in Rat Lung Following Thoracic X-irradiation

Abstract

The temporal patterns of several responses in the lungs of groups of rats administered two different thoracic doses of X-rays (7.5 and 15 Gy) were examined during a time frame within which radiation pneumonitis develops (1-13-week period) in order to assess for potential interrelationships among the responses. Endpoints surveyed included lung gravimetric and volumetric changes, changes in lavaged alveolar macrophage (AM) numbers, interstitial accumulations of mast cells (MC), and alterations in the amounts of lavaged phospholipids (PL), protein (P), and histamine (H). Sham-irradiated rats served as controls. Early (1 week), dose-dependent increases in lavageable PL were not accompanied by increases in lung weights or lavageable P. Elevations in lavaged PL continued for at least 5 weeks after exposure. By this time, lung weights, AM numbers, MC, and lavageable P, but not lavageable H, were all substantially increased in lungs that received the 15 Gy dose, whereas these changes were not observed at the lower dose. At later times (weeks 7 and 9), the hyperpermeability response following the 15 Gy exposure became less pronounced and the PL response also subsided, while lung MC continued to further increase and lavageable H became abnormally elevated. Maximal increases in the lung's permeability status after the 15 Gy exposure was coincidental with maximal increases in AM. An association of increases in AM and lung hyperpermeability, however, was not evident as of week 13 after the 7.5 Gy dose when lung weights and lavageable P were significantly elevated. For the X-ray doses examined, our results suggest that: (1) the early PL response to X-rays is independent of, and precedes, permeability changes in the lung; (2) the time to onset of an X-irradiation-induced increase in lung permeability is dose-dependent; (3) the progressive accumulation of MC in the lung following X-irradiation is dose-dependent; (4) excessive accumulations of interstitial MC after X-irradiation do not necessarily result in an increase in free H; and (5) free H in the lung does not appear to play a prominent role in the hyperpermeable response. Additionally, in conjunction with the findings of other investigators, our study suggests that the MC response to X-rays may be a fundamental component of the fibrogenic response.

The production of collagen and the activity of mast‐cell chymase increase in human skin after irradiation therapy

“…The role of mast cells in radiation‐induced fibrosis has previously been studied in animal models. In rat lung, the number of mast cells has been found to be increased as a result of irradiation (48,49), although contradictory results have also been observed (50).…”

Effects of IL-4 on pulmonary fibrosis and the accumulation and phenotype of macrophage subpopulations following thoracic irradiation

“…Following high total (single or fractionated) doses, this results in an accumulation of activated macrophages and lymphocytes in the irradiated tissue that in turn can regulate the inflammatory and wound healing response (Lehnert et al, 1991, Paun et al, 2015, Wesselius and Kimler, 1989). The regulatory mechanisms that mediate this injury response therefore evolve over the various phases of inflammation and repair.…”

Low Dose Radiation-induced Endothelial Cell Retraction

“…2 days to 2-3 weeks post-irradiation (Gross 1977, Lehnert et al 1991 . The time course between lethal exposure and denudation or loss of vascular integrity has usually been found to be approx .…”