TY - JOUR
T1 - Role of the eosinophil in chronic vascular rejection of renal allografts
AU - Nolan, Charles R.
AU - Saenz, Kristin P.
AU - Thomas, Charles A.
AU - Murphy, Kim D.
N1 - Funding Information:
The authors am grateful to Hanna E. Abboud, MD, for his support and insightful review of the manuscript. Roberto Estrada and Rudy Villarreal provided expert technical assistance. Dr Uhich 0. Wenzel supplied the human renal artery smooth muscle cells. Dr David T. Wong graciously provided details regarding the Fisher-Giemsa staining technique. Reproduction of color figures was made possible through educational grants from Fujisawa Pharmaceutical Co and Sandoz Pharmaceutical Corp.
Funding Information:
Presented in abstract form at the 27th Annual Meeting of the American Society of Nephrology, Orlando, FL, October 1994. Supported in part by a grant from the Southern Arizona Foundation, Tucson, AZ. Dr Nolan is the recipient of the DonaldSeldin, MD, Young Investigator Grant of the National Kidney Foundation, New York, NY (1994-1996).
PY - 1995/10
Y1 - 1995/10
N2 - Obliterative arteriopathy in chronic renal allograft rejection is caused by intimal smooth muscle proliferation accompanied by infiltration of lymphocytes, monocytes, and eosinophils. We investigated the role of the eosinophil in chronic rejection. Twenty-four allograft nephrectomies were examined for the presence of eosinophils on hematoxylin-eosin-stained sections and using epifluorescence on Fisher-Giemsa-stained sections. Among 15 cases with chronic rejection, eosinophils were detected in 14 cases (93%) with epifluorescence compared with only six cases (40%) with hematoxylin-eosin staining (P = 0.005). With epifluorescence, eosinophils were identified in the intimal, adventitial, and tubulointerstitial compartments in 73%, 80%, and 87% of cases, respectively. To examine the pathogenic relevance of the eosinophils in the vessel wall, we investigated the effect of eosinophil-conditioned medium on DNA synthesis in cultured vascular smooth muscle cells. Autofluorescent eosinophils were isolated from atopic human donors using a fluorescence-activated cell sorter. Supernatant was collected from eosinophils (1 × 106/mL) cultured overnight in medium with 0.5% fetal bovine serum. Incorporation of 3H-thymidine into DNA was measured in rat and human vascular smooth muscle cells treated for 24 hours with eosinophil-conditioned medium at 1:20, 1:10, 1:5, and 1:2 dilutions. Eosinophil-conditioned medium had a significant dose-dependent stimulatory effect on DNA synthesis in both cell lines. Our results indicate that eosinophil involvement in chronic renal allograft rejection is more common than previously recognized. The stimulatory effect of eosinophil-conditioned medium on vascular smooth muscle cell DNA synthesis suggests that eosinophils may be involved in the pathogenesis of the obliterative arteriopathy characteristically seen in chronic vascular rejection of renal allografts.
AB - Obliterative arteriopathy in chronic renal allograft rejection is caused by intimal smooth muscle proliferation accompanied by infiltration of lymphocytes, monocytes, and eosinophils. We investigated the role of the eosinophil in chronic rejection. Twenty-four allograft nephrectomies were examined for the presence of eosinophils on hematoxylin-eosin-stained sections and using epifluorescence on Fisher-Giemsa-stained sections. Among 15 cases with chronic rejection, eosinophils were detected in 14 cases (93%) with epifluorescence compared with only six cases (40%) with hematoxylin-eosin staining (P = 0.005). With epifluorescence, eosinophils were identified in the intimal, adventitial, and tubulointerstitial compartments in 73%, 80%, and 87% of cases, respectively. To examine the pathogenic relevance of the eosinophils in the vessel wall, we investigated the effect of eosinophil-conditioned medium on DNA synthesis in cultured vascular smooth muscle cells. Autofluorescent eosinophils were isolated from atopic human donors using a fluorescence-activated cell sorter. Supernatant was collected from eosinophils (1 × 106/mL) cultured overnight in medium with 0.5% fetal bovine serum. Incorporation of 3H-thymidine into DNA was measured in rat and human vascular smooth muscle cells treated for 24 hours with eosinophil-conditioned medium at 1:20, 1:10, 1:5, and 1:2 dilutions. Eosinophil-conditioned medium had a significant dose-dependent stimulatory effect on DNA synthesis in both cell lines. Our results indicate that eosinophil involvement in chronic renal allograft rejection is more common than previously recognized. The stimulatory effect of eosinophil-conditioned medium on vascular smooth muscle cell DNA synthesis suggests that eosinophils may be involved in the pathogenesis of the obliterative arteriopathy characteristically seen in chronic vascular rejection of renal allografts.
KW - Eosinophil
KW - chronic rejection
KW - epifluorescence microscopy
KW - thymidine incorporation
KW - vascular smooth muscle
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U2 - 10.1016/0272-6386(95)90601-0
DO - 10.1016/0272-6386(95)90601-0
M3 - Article
C2 - 7573019
AN - SCOPUS:0029149877
VL - 26
SP - 634
EP - 642
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 4
ER -