Leukocyte accumulation in graft blood vessels during self-limiting acute rejection of rat kidneys

• Published in: Immunobiology (1979) Vol. 216; no. 5; pp. 613 - 624
• Main Authors: Zakrzewicz, Anna, Wilhelm, Jochen, Blöcher, Sonja, Wilczynska, Joanna, Wilker, Sigrid, Dietrich, Hartmut, Weimer, Rolf, Padberg, Winfried, Grau, Veronika
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.05.2011
• Subjects: Acute Disease; Acute rejection; Advanced Basic Science; Allergy and Immunology; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Blood; Chronic rejection; Cytokines - genetics; Cytokines - metabolism; Gene Expression Profiling; Gene Expression Regulation; Graft Rejection - immunology; Kidney - blood supply; Kidney - pathology; Kidney Transplantation; Lymphocyte Activation - genetics; Monocyte; Monocytes - immunology; Monocytes - metabolism; Monocytes - pathology; Rats; Rats, Inbred F344; Rats, Inbred Lew; Renal transplantation; Transplantation, Homologous - immunology; Transplantation, Homologous - pathology; chronic allograft nephropathy; DAB; Fischer 344; tissue factor; Monocyte; H&E; qRT-PCR; Chronic rejection; quantitative real-time RT-PCR; F344; Blood; mAb; azocarmine/aniline blue; AR; CAN; TF; 3,3′diaminobenzidine; hemalum eosin; acute rejection; Lewis; Renal transplantation; Azan; monoclonal antibody; LEW; Acute rejection
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2010.09.009

Abstract During self-limiting acute rejection preceding chronic vasculopathy, large amounts of leukocytes, predominantly monocytes, interact with the endothelium of renal allografts. We aim to characterize them and to identify targets for functional and interventional studies. Leukocytes were harvested by vascular perfusion from Fischer 344 to Lewis renal allografts or Lewis isografts, followed by flow cytometry, quantitative RT-PCR and genome-wide transcriptional profiling. Leukocyte accumulation peaked in allografts on day 9. The percentage of monocytes expressing MHC class II and CD161 was increased whereas CD4, CD11a, CD43, and CD71 expression remained unchanged. IFN-γ, IL-1β, IL-2, IL-10, TNF-α, and iNOS mRNA increased in allograft leukocytes but IL-4, IL-6, IL-12, TGF-β, and tissue factor did not. During acute rejection, 1783 genes were differentially expressed. In conclusion, graft blood leukocytes display a unique state of partial activation during self-limiting rejection. Numerous differentially expressed genes deserve further investigation as potential factors in deciding the fate of the allograft.