Fractalkine: an important candidate for directing periglomerular leukocyte accumulation in irradiated mouse kidneys.
Radiation-induced impairment of renal function is preceded by capillary endothelial cell damage, which initiates a cascade of inflammatory and thrombotic events. Accumulation of leukocytes in the irradiated kidney, especially in areas surrounding the glomeruli, has been clearly demonstrated. The chemokine fractalkine has recently been identified as a key mediator of leukocyte adhesion that functions without the requirement of integrins or selectin-mediated rolling. In this study we investigate the possible involvement of fractalkine in the inflammatory response of the irradiated kidney. Mouse kidneys were irradiated with single doses of 16 or 0 Gy, and protein and mRNA levels of fractalkine and PECAM-1 were examined after 10 to 40 weeks. These changes were correlated with the progressive increase and distribution of leukocytes in the irradiated kidneys. Increased fractalkine immunoreactivity was seen at glomerular sites 30 to 40 weeks after irradiation. This fractalkine expression was strongly associated with the presence of leukocytes surrounding the Bowman's capsule of the same glomeruli. No significant changes in mRNA levels of fractalkine were seen in whole kidney extracts after irradiation, but expression levels were not determined for isolated glomeruli. PECAM-1 protein levels did not change with time after irradiation, although a significant decrease in mRNA expression was seen at 10 weeks. This study is the first demonstration of increased fractalkine after irradiation and the results suggest that fractalkine may be an important mechanism of leukocyte trafficking in the development of a radiation induced inflammatory response.
Kruse
Jacqueline J C M
JJ
The Netherlands Cancer Institute, Division of Experimental Therapy (H6), Amsterdam, The Netherlands.
Bomhoff-Wijdenes
Inge F M
IF
Poele
Johannes A M Te
JA
Stewart
Fiona A
FA
D000818:Animals; D054428:Chemokine CX3CL1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000528:radiation effects*; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology* / Q000276:immunology; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000737:chemistry / Q000276:immunology* / Q000528:radiation effects*; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011832:Radiation Injuries / Q000209:etiology* / Q000276:immunology
D054428:Chemokine CX3CL1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger