Influence of rapamycin on rat macrophage viability and chemotaxis toward allogenic pancreatic islet supernates.
The aim of this work was to evaluate the effects of rapamycin on rat macrophage viability and chemotaxis toward allogereic pancreatic islet supernates. Macrophages were isolated from rats by peritoneal lavage at 3 days after intraperitoneal injection of thioglycolate. Macrophage viability was studied after 7 days of culture by Cell Titer assays in the presence of rapamycin at 0.1, 1, and 10 ng/mL (n = 6). After 48 hours of culture, pancreatic rat islet supernates were studied for there chemotactic properties toward freshly isolated macrophages in the presence of rapamycin at 0.1, 1, and 10 ng/mL. Chemotaxis was expressed as a migration index defined as the number of macrophages attracted by the test solution (islet supernate +/- rapamycin)/number of macrophages attracted by the supernate (n = 6). After 3 days of culture, macrophage viability decreased significantly by 22%, 36%, and 32% in the presence of 0.1, 1, and 10 ng/mL rapamycin, respectively (P = .008). Macrophage viability remained stable at about 70% after 7 days of culture. In the presence of islet supernates, macrophage migration increased two-fold compared with those obtained by culture medium. Rapamycin did not influence macrophage migration toward culture medium. However, the drug significantly reduced the migration of macrophages toward islet supernates from 2 +/- 0.6 to 0.9 +/- 0.4, 0.7 +/- 0.3, or 0.8 +/- 0.4 in the presence of 0.1, 1, or 10 ng/mL rapamycin, respectively (P = .04). Rapamycin decreased the survival of cultured rat macrophages and their migration toward allogenic islet supernates. These results suggested that, besides its anti-proliferative effect on T cells, rapamycin reduced macrophage attraction to the graft site.
Danner
S
S
Laboratoire de Thérapie Cellulaire et Génique du Diabète, Centre Européen d'Etude du Diabète, Strasbourg, France.
Sigrist
S
S
Moreau
F
F
Mandes
K
K
Vodouhé
C
C
Langlois
A
A
Soskin
S
S
Fichbach
M
M
Pinget
M
M
Kessler
L
L
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D003470:Culture Media; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous
D003470:Culture Media; D020123:Sirolimus