Possible involvement of urokinase-type plasminogen activator release from human peripheral blood lymphocytes in the pathophysiology of chronic allograft nephropathy.
BACKGROUND
Little is known of the fibrinolytic host immune mechanisms responsible for induction of chronic allograft nephropathy (CAN), defined as a loss in glomerular filtration rate (GFR) caused by tubular atrophy and interstitial fibrosis, often with fibrous intimal thickening in the small arteries. However, chronic rejection has been reported to be associated with decreased activity of the fibrinolytic system. In our previous study, [Deamino-Cys1, D-Arg8]-vasopressin (dDAVP) induced urokinase-type plasminogen activator (uPA) release from human peripheral T lymphocytes via arginine vasopressin (AVP) V2-receptor-mediated reaction enhanced by an AVP V1-receptor antagonist. Therefore, we examined the level of uPA released from peripheral T lymphocytes by AVP in transplant patients with CAN in comparison with control groups.


METHODS
In this study, we evaluated in vitro uPA releasing activity of lymphocytes obtained from renal allograft patients with well-functioning grafts (n = 9), CAN (n = 5), or acute rejection episodes (n = 5) compared with lymphocytes from healthy volunteers with normal renal function (n = 12) or patients with renal insufficiency (n = 5).


RESULTS
Lymphocytes prepared from patients with chronic allograft nephropathy showed a significantly lower increase in uPA release induced by the combination of the V1-receptor antagonist and dDAVP compared with those from the other groups.


CONCLUSIONS
This finding suggested that a decrease in uPA release from human peripheral blood lymphocytes by AVP-related peptides may be potentially involved in the pathophysiology of CAN.
Yamaguchi
Y
Y
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Suzuki
T
T
Arita
S
S
Iwashita
C
C
Sakamoto
K
K
Hatakeyama
E
E
Shimmura
H
H
Tanabe
K
K
Ichinose
M
M
Suzuki
N
N
Yamada
K
K
D000328:Adult; D001127:Arginine Vasopressin / Q000502:physiology; D002908:Chronic Disease; D003894:Deamino Arginine Vasopressin / Q000097:blood; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood*
D001127:Arginine Vasopressin; D014568:Urokinase-Type Plasminogen Activator; D003894:Deamino Arginine Vasopressin