Suppression of allograft rejection in the sponge Suberites domuncula by FK506 and expression of genes encoding FK506-binding proteins in allografts.
Porifera (sponges) are, evolutionarily, the oldest metazoan phylum. Recent molecular data suggest that these animals possess molecules similar to and homologous with those of the innate and adaptive immune systems of higher Metazoa. Applying the biological system of parabiosis and the technique of differential display of mRNA, two cDNAs encoding putative FK506-binding proteins were isolated. FK506 is successfully used in clinics as a drug to prevent allograft rejection and is toxic to Suberites domuncula cells in vitro at doses above 100ng ml(-1). Autograft fusion of transplants from S. domuncula was not affected by FK506. Allograft non-fusion was not affected by FK506 at toxic doses; however, at the non-toxic dose of 20ng ml(-1), the allografts fused with each other. It is shown that at the attachment zone in untreated and (particularly drastic) in FK506-treated allografts, expression of the genes encoding the FK506-binding proteins is upregulated. These data indicate that the drug FK506 suppresses allograft rejection in S. domuncula, most probably via interaction with expression of the gene coding for the FK506-binding proteins.
Müller
W E
WE
Institut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universität, Duesbergweg 6, D-55099 Mainz, Germany. WMUELLER@mail.UNI-Mainz.DE
Steffen
R
R
Lorenz
B
B
Batel
R
R
Kruse
M
M
Krasko
A
A
Müller
I M
IM
Schröder
H C
HC
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D015723:Gene Library; D006084:Graft Rejection / Q000517:prevention & control; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011161:Porifera / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D017385:Sequence Homology; D016559:Tacrolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000235:genetics*; D014184:Transplantation, Homologous / Q000276:immunology
D018076:DNA, Complementary; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus