| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
RI and TLR-Mediated Mast Cell Activation1
* Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Ionizing gamma radiation has several therapeutic indications including bone marrow transplantation and tumor ablation. Among immune cells, susceptibility of lymphocytes to gamma radiation is well known. However, there is little information on the effects of gamma radiation on mast cells, which are important in both innate and acquired immunity. Previous studies have suggested that mast cells may release histamine in response to high doses of gamma radiation, whereas other reports suggest that mast cells are relatively radioresistant. No strong link has been established between gamma radiation and its effect on mast cell survival and activation. We examined both human and murine mast cell survival and activation, including mechanisms related to innate and acquired immune responses following gamma radiation. Data revealed that human and murine mast cells were resistant to gamma radiation-induced cytotoxicity and, importantly, that irradiation did not directly induce β-hexosaminidase release. Instead, a transient attenuation of IgE-mediated β-hexosaminidase release and cytokine production was observed which appeared to be the result of reactive oxygen species formation after irradiation. Mast cells retained the ability to phagocytose Escherichia coli particles and respond to TLR ligands as measured by cytokine production after irradiation. In vivo, there was no decrease in mast cell numbers in skin of irradiated mice. Additionally, mast cells retained the ability to respond to Ag in vivo as measured by passive cutaneous anaphylaxis in mice after irradiation. Mast cells are thus resistant to the cytotoxic effects and alterations in function after irradiation and, despite a transient inhibition, ultimately respond to innate and acquired immune activation signals.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and the National Cancer Institute, Center for Cancer Research.
2 B.P.S. and J.M.B. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Jared M. Brown, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C209, 10 Center Drive, MSC 1881, Bethesda, Maryland 20892-1881. E-mail address: jmbrown{at}niaid.nih.gov
4 Abbreviations used in this paper: ARS, acute radiation syndrome; BMMC, bone marrow-derived mast cell; HuMC, human-derived mast cell; HSA, human serum albumin; poly(I:C), polyinosinic-polycytidylic acid; ROS, reactive oxygen species; DCF, dichlorofluorescein; PCA, passive cutaneous anaphylaxis; LDH, lactate dehydrogenase; BMT, bone marrow transplantation.
This article has been cited by other articles:
|
|
 |
|
  S. Zarini, M. A. Gijon, A. E. Ransome, R. C. Murphy, and A. Sala Transcellular biosynthesis of cysteinyl leukotrienes in vivo during mouse peritoneal inflammation PNAS, May 19, 2009; 106(20): 8296 - 8301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Burke, T. B. Issekutz, K. Mohan, P. W. K. Lee, M. Shmulevitz, and J. S. Marshall Human mast cell activation with virus-associated stimuli leads to the selective chemotaxis of natural killer cells by a CXCL8-dependent mechanism Blood, June 15, 2008; 111(12): 5467 - 5476. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
