Radiation-induced normal tissue injury: role of adhesion molecules in leukocyte-endothelial cell interactions.
The late onset of necrosis and fibrosis in normal tissues can be a serious consequence of radiotherapy in cancer patients. Because radiation-induced vascular injury precedes the tissue damage, vascular injury is regarded as crucial in the pathogenesis of tissue damage. An understanding of the processes responsible is essential to develop strategies for the amelioration of radiation-induced normal tissue damage. Leukocyte infiltration is commonly observed at sites of irradiation and is likely to lead to the acceleration and/or induction of parenchymal atrophy, fibrosis and necrosis in normal tissues following radiotherapy. The molecular mechanisms mediating leukocyte infiltration of tissues during inflammation have been studied extensively. It is now well established that cell adhesion molecules (CAMs) expressed on leukocytes and endothelial cells control the trafficking of leukocytes from the blood vessel lumen in these conditions. CAMs including E (endothelial), P (platelet) and L (leukocyte)-selectins, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), beta1 and beta2 integrins and CD31 are involved in the cascade of events resulting in rolling, arrest and transmigration of leukocytes through the inflamed endothelium. Whether a similar sequence of molecular events induces leukocyte sequestration in irradiated normal tissues is not known. This review is focussed on the role of CAMs in radiation-induced leukocyte infiltration of normal tissues and the therapeutic implications of these findings.
Department of Pathological Sciences, Manchester University and Christie Hospital, UK.
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Quarmby
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Kumar
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Kumar
D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002450:Cell Communication / Q000528:radiation effects*; D002453:Cell Cycle / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D007962:Leukocytes / Q000473:pathology / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*
D015815:Cell Adhesion Molecules