Perturbation of endothelial functions by ionizing irradiation: effects on prostaglandins, chemoattractants and mitogens.
Numerous studies have shown that early radiation injury is characterized by vascular damage and that the initial site of damage appears to be the EC lining of the vessel wall. Chronic irreversible tissue reactions to radiation include thrombotic occlusion of capillaries, enhanced atherosclerosis in larger vessels, inflammatory changes, and late tissue fibrosis. These processes may be mediated by endothelial products released as a result of cellular injury. Using EC cultures, we show that ionizing irradiation affects one of the major vascular defense mechanisms against platelet activation, thrombosis, and atherosclerosis--the capacity to produce PGI2. Dose- and time-related damage to enzymes of the arachidonic acid cascade were demonstrated. Radiation damage is associated with oxidant stress and production of free radicals. The oxygen radical scavenger, vitamin C, was found to protect the capacity of irradiated ECs to produce PGI2. Radiation injury often induces an acute inflammatory response. We found that irradiated ECs release a chemotactic factor for neutrophils, which is a lipid product of the lipoxygenase pathway. Late radiation-induced tissue fibrosis and the capacity of radiation to enhance arteriosclerosis may involve participation of mitogens released from perturbed and damaged ECs. We show that conditioned medium of irradiated ECs contain larger amounts of newly synthesized mitogens capable of stimulating the proliferation of fibroblasts, SMCs, and ECs. Hence, it may be assumed that the mitogenic activity released by irradiated ECs includes both PDGF and FGF-like mitogens.
Eldor
A
A
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Fuks
Z
Z
Matzner
Y
Y
Witte
L D
LD
Vlodavsky
I
I
D000818:Animals; D002417:Cattle; D002630:Chemotactic Factors / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000528:radiation effects; D004261:DNA Replication / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000528:radiation effects*; D011464:Epoprostenol / Q000378:metabolism*; D008934:Mitogens / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000378:metabolism*
D002630:Chemotactic Factors; D008934:Mitogens; D011464:Epoprostenol