Activation of macrophage-associated molecules after brain death in islets.
Islet transplantation is now established as an optional treatment for type I diabetes. However, rates of insulin independence in islet transplant recipients are still low. Although the major source of allograft is derived from brain-dead patient, the nonphysiologic state of brain death (BD) deteriorates organs such as liver and kidney. To determine the effects of BD on islets, a rodent model of BD has been used. Histologically, islets of BD rats showed decreased permeability and impaired integrity of the cell membranes. Flow cytometric analysis showed that CD11b/c-positive cells within islets were slightly increased in BD. This result suggests that BD induces macrophage infiltration into the islets. Moreover, RT-PCR revealed significant augmentation of macrophages-associated inflammatory molecules (IL-1beta, IL-6, TNF-alpha, and MCP-1) in islets from a BD donor. Inducible nitric oxide synthase (iNOS) was weakly expressed, although not reaching statistical significance compared with control. Our results indicate that islets from a BD donor are immunologically activated and have a potential risk factor for early graft loss and a poor long-term function of grafts in clinical setting of islet transplantation. Immunomodulation, to eliminate intraislet immunocytes and/or activated macro phage-associated molecules, might be necessary for the better outcome after islet graft from BD donors.
Toyama
Hirochika
H
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kobe University, Kobe, Japan.
Takada
Moriatsu
M
Suzuki
Yasuyuki
Y
Kuroda
Yoshikazu
Y
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D001926:Brain Death / Q000473:pathology / Q000503:physiopathology*; D018845:CD11 Antigens / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology*; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects* / Q000379:methods*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow / Q000276:immunology; D014019:Tissue Donors
D000276:Adjuvants, Immunologic; D018845:CD11 Antigens; D016207:Cytokines; D009569:Nitric Oxide