Absence of CSF-1-dependent macrophages does not improve function of transplanted islets of Langerhans.
A role of macrophage-mediated inflammatory events in early islet graft loss is increasingly acknowledged. Osteopetrotic mice (op/op) have a complete absence of CSF-1, and thus of most tissue macrophages. We have investigated whether the absence of CSF-1-dependent macrophages in the graft itself or at the transplant site could decrease the delay to function of a syngeneic marginal islet mass. Islets transplanted into op/op or control recipients reversed diabetes in 59 days vs. 10 days (p = 0.28, NS). Islets isolated from op/op or control mice reversed diabetes in 11 days vs. 10 days. IL-1 and TNF-alpha release by cultured islets was markedly decreased for op/op islets compared with control islets (IL-1: 0 vs. 4.2 pg/ml, p = 0.07; TNF-alpha: 67 vs. 311 pg/ml, p = 0.002). In contrast, IL-6 release by op/op islets was significantly increased (11.1 vs. 4.3 ng/ml, p = 0.006). CSF-1-dependent tissue macrophages may not be critical in the inflammatory insult to islet transplants. Alternate patterns of intraislet release of deleterious proinflammatory cytokines may exist.
Berney
T
T
Diabetes Research Institute, University of Miami Medical School, FL 33136, USA.
Molano
R D
RD
Pileggi
A
A
Cattan
P
P
Vizzardelli
C
C
Ricordi
C
C
Inverardi
L
L
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010022:Osteopetrosis / Q000235:genetics* / Q000276:immunology
D016173:Macrophage Colony-Stimulating Factor