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


METHODS
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.


RESULTS
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.


CONCLUSIONS
We propose that ionizing radiation leads to a degranulation of dermal mast cells, an event which is accompanied by the release of tryptase.
Albrecht
Martin
M
Anatomisches Institut am Biederstein, Ludwig-Maximilians-Universität, Munich, Germany.
Müller
Kerstin
K
Köhn
Frank M
FM
Meineke
Viktor
V
Mayerhofer
Artur
A
D015550:Cell Degranulation / Q000502:physiology / Q000528:radiation effects*; D002478:Cells, Cultured; D017332:Cetirizine / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis / Q000150:complications / Q000473:pathology; D005434:Flow Cytometry; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008407:Mast Cells / Q000201:enzymology / Q000528:radiation effects*; D012515:Mast-Cell Sarcoma / Q000000981:diagnostic imaging* / Q000473:pathology; D011839:Radiation, Ionizing; D011877:Radionuclide Imaging; D012867:Skin / Q000166:cytology / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors; D053802:Tryptases / Q000378:metabolism / Q000528:radiation effects*
D006634:Histamine H1 Antagonists; D053802:Tryptases; D017332:Cetirizine