Blockade of CD47 increases survival of mice exposed to lethal total body irradiation

• Published in: Scientific reports Vol. 3; no. 1; p. 1038
• Main Authors: Soto-Pantoja, David R., Ridnour, Lisa A., Wink, David A., Roberts, David D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.01.2013; Nature Publishing Group
• Subjects: 631/154/555; 631/67; 692/308/2778; 692/308/575; Accidents; Acute Radiation Syndrome - drug therapy; Acute Radiation Syndrome - prevention & control; Animals; Antisense therapy; Blood Cell Count; Bone marrow; Bone Marrow - radiation effects; Bone Marrow Cells - drug effects; Bone Marrow Cells - radiation effects; CD47 Antigen - genetics; CD47 Antigen - metabolism; Cell death; Cell Death - drug effects; Cell Proliferation - drug effects; Esophagus - drug effects; Esophagus - radiation effects; Humanities and Social Sciences; Intestinal Mucosa - drug effects; Intestinal Mucosa - radiation effects; Ionizing radiation; Irradiation; Mice; Mice, Inbred C57BL; Morpholinos - administration & dosage; Morpholinos - pharmacology; Morpholinos - therapeutic use; multidisciplinary; Nuclear accidents & safety; Phagocytosis; Radiation protection; Radiation Tolerance - drug effects; Radiation-Protective Agents - administration & dosage; Radiation-Protective Agents - pharmacology; Radiation-Protective Agents - therapeutic use; Science; Soft tissues; Survival; Terrorism; Thrombospondin; Thrombospondin 1 - antagonists & inhibitors; Transcription Factors - biosynthesis; Whole-Body Irradiation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep01038

Accidental or therapeutic total body exposure to ionizing radiation has profound pathophysiological consequences including acute radiation syndrome. Currently only investigational drugs are available in case of radiological or nuclear accidents or terrorism. Lack of selective radioprotectants for normal tissues also limits the therapeutic doses that can be delivered to treat cancers. CD47 is a receptor for the secreted protein thrombospondin-1. Blockade of thrombospondin-1 or CD47 provides local radioprotection of soft tissues and bone marrow. We now report that suppression of CD47 using an antisense morpholino increases survival of mice exposed to lethal total body irradiation. Increased survival is associated with increased peripheral circulating blood cell counts and increased proliferative capacity of bone marrow derived cells. Moreover, CD47 blockade decreased cell death while inducing a protective autophagy response in radiosensitive gastrointestinal tissues. Thus, CD47 is a new target for radiomitigation that prevents both hematopoietic and gastrointestinal radiation syndromes.