title: Absence of CSF-1-dependent macrophages does not improve function of transplanted islets of Langerhans.
abstract: 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.
authors.affiliation: Diabetes Research Institute, University of Miami Medical School, FL 33136, USA.
authors.forename: T
authors.initials: T
authors.lastname: Berney
authors.forename: R D
authors.initials: RD
authors.lastname: Molano
authors.forename: A
authors.initials: A
authors.lastname: Pileggi
authors.forename: P
authors.initials: P
authors.lastname: Cattan
authors.forename: C
authors.initials: C
authors.lastname: Vizzardelli
authors.forename: C
authors.initials: C
authors.lastname: Ricordi
authors.forename: L
authors.initials: L
authors.lastname: Inverardi
mesh_terms: 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
chemical_list: D016173:Macrophage Colony-Stimulating Factor