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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Antigens, Differentiation, CD4-Positive T-Lymphocytes, Calcium, Cell Communication, Cell Movement, Disease Progression, Enzyme Activation, Gene Expression Regulation, Graft Rejection, Histocompatibility Antigens, Immunization, Lymphocyte Activation, Macrophage Activation, Macrophages, Peritoneal, Male, Nitric Oxide Synthase Type II, Peptide Fragments, Rats, Rats, Inbred Lew, Rats, Inbred WF, Thyroid Gland, Transplantation, Homologous.
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Does analysis of parathyroid graft rejection suggest alloantigen-specific production of nitric oxide by iNOS-positive intragraft macrophages? Context: During acute rejection of organ or tissue allografts T cells and macrophages are dominant infiltrating cells. CD4-positive T cells are important for the induction of allograft rejection and macrophages are important effector cells mediating cytotoxicity via production of nitric oxide (NO) by the inducible NO-synthase (iNOS). In the present study we analysed whether the destruction of primarily nonvascularised parathyroid allografts is also mediated by iNOS-positive macrophages. Hypocalcaemic Lewis rats received parathyroid isografts (from Lewis donors) and allografts (from Wistar Furth donors), respectively, under the kidney capsule. Levels of serum calcium above 2 mmol/L correlated with normal parathyroid function and below 2 mmol/L with parathyroid rejection. Accelerated parathyroid allograft rejection was induced by immunisation of Lewis recipients with the allogeneic peptide P1. Determination of serum calcium levels is a useful parameter to control parathyroid graft function, and therefore to determine allograft rejection. Macrophages positive for both major histocompatibility complex (MHC) class II molecules and costimulatory molecules accumulated in iso- and allografts, but iNOS-positive macrophages were only detectable in allografts in the presence of activated CD4-positive T cells. These results confirm a cooperation between activated T cells and intragraft macrophages to induce macrophage iNOS expression. Recipients immunised with the allogeneic peptide P1 demonstrated accelerated rejection of allografts (mean+/-SD: 9.2+/-0.9 days) in contrast to nonimmunised animals (mean+/-SD: 15.8+/-1.8 days). Allografts of P1-immunised animals were infiltrated faster by activated CD4-positve T cells and, in addition, the infiltrates of iNOS-positive macrophages were stronger than those in allografts of nonimmunised animals.
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Intragraft iNOS-positive macrophages seem to be able to produce cytotoxic NO involved in the killing of allogeneic cells during the alloimmune response against primarily nonvascularised parathyroid organ grafts. Infiltrates of iNOS-negative macrophages found in parathyroid isografts were caused by antigen-independent inflammation triggered by surgically induced injury. The absence of activated T cells in isografts and their presence in allografts underlines their importance in inducing macrophage iNOS expression. Final Decision: yes