Ionizing radiation induces degranulation of human mast cells and release of tryptase

Skin fibrosis is a hallmark of ionizing radiation-induced tissue injury and we hypothesized that mast cells via their products (especially tryptase) are involved in this event. We therefore investigated whether: (i) irradiation with 5 Gray (Gy) is able to induce the release of the typical mast cell mediator tryptase from human mast cells (HMC-1) in vitro, (ii) this effect can be influenced by application of clinically relevant mast cell blockers, and (iii) irradiation leads to mast cell degranulation in ex vivo skin culture models.

The human mast cell line (HMC)-1, as well as ex vivo skin tissue served as experimental models. Fluorescence activated cell sorting (FACS), Enzyme linked immunosorbent assays (ELISA), mast cell degranulation assays and immunohistochemistry were applied.

Ionizing radiation induces a time-dependent, statistically significant increase in the release of tryptase by HMC-1 cultured in vitro. Mast cell degranulation and secretion of tryptase was partially, but not significantly, inhibited by pre-incubation with the histamine-1 receptor (H1) blocker cetirizine. Mast cell degranulation was also clearly evident after irradiation using an ex vivo skin culture model of mastocytoma tissue.

We propose that ionizing radiation leads to a degranulation of dermal mast cells, an event which is accompanied by the release of tryptase.