Antagonists of cyclic nucleotide phosphodiesterase (PDE) isozymes PDE 3 and PDE 4 suppress lymphoblastic response to HLA class II alloantigens: a potential novel approach to preventing allograft rejection?
As a potential novel approach to preventing renal allograft rejection, we investigated whether the proliferative response of lymphocytes to mismatched HLA class II antigens in mixed lymphocytic culture (MLC) can be suppressed by antagonists of cyclic nucleotide phosphodiesterase (PDE) isozymes. Cilostamide, an antagonist of isozyme PDE3 and, to an even greater extent, in combination with rolipram, an antagonist of isozyme PDE4, markedly suppressed (delta = -60%; p < 0.01) the mitogenic proliferative response of lymphocytes in MLC to HLA-DR alloantigens from unrelated donors. These observations suggest that the selective PDE isozyme antagonists might have potential as novel drugs in "signal transduction-targeted" pharmacotherapy of renal transplant rejection.
Dousa
M K
MK
Department of Laboratory Medicine, Mayo Clinic and Foundation, MN 55905, USA.
Moore
S B
SB
Ploeger
N A
NA
DeGoey
S R
SR
Dousa
T P
TP
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006084:Graft Rejection / Q000517:prevention & control*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D020889:Rolipram
D000949:Histocompatibility Antigens Class II; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D015363:Quinolones; C021294:cilostamide; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram