Xenogeneic skin graft rejection in M-CSF/macrophage deficient osteopetrotic mice

• Published in: Xenotransplantation (Københaven) Vol. 10; no. 3; pp. 232 - 239
• Main Authors: Zhao, Yong, Xiong, Wanfen, Yang, Tianyu, Prall, Amy, Baxter, B. T., Langnas, Alan N.
• Format: Journal Article
• Language: English
• Published: Oxford UK Munksgaard International Publishers 01.05.2003
• Subjects: Animals; graft rejection; Graft Survival - immunology; immune response; Immunity, Cellular; Lymphocyte Culture Test, Mixed; macrophage; Macrophage Colony-Stimulating Factor - deficiency; Macrophage Colony-Stimulating Factor - genetics; Macrophage Colony-Stimulating Factor - physiology; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Osteopetrosis - genetics; Rats; Skin Transplantation - immunology; Skin Transplantation - pathology; Spleen - immunology; T-Lymphocytes - immunology; Time Factors; Transplantation, Heterologous - immunology; Transplantation, Homologous; xenotransplantation
• ISSN: 0908-665X; 1399-3089
• DOI: 10.1034/j.1399-3089.2003.01142.x

Zhao Y, Xiong W, Yang T, Prall A, Baxter BT, Langnas AN. Xenogeneic skin graft rejection in M‐CSF/macrophage deficient osteopetrotic mice. Xenotransplantation 2003; 10: 232–239. © Blackwell Munksgaard, 2003 Background: The cellular infiltrate in xenografts suggests that macrophages may be involved in xenograft rejection. However, the precise role of macrophages in xenograft rejection has not yet been fully addressed. Methods: Xenogeneic rat skin grafts were transplanted to macrophage colony stimulating factor (M‐CSF)/macrophage‐deficient osteopetrotic ([OP]–/–) and wild‐type control mice. Skin graft survival and antidonor rat humoral responses were quantified. Results: Xenogeneic rat skin grafts survived 13 days in wild‐type control mice, survival of rat skin grafts was significantly prolonged to 24 days in [OP]–/– mice (P<0.01). Similar results were observed in sensitized [OP]–/– and control mouse recipients, showing markedly prolonged rat skin graft survival in [OP]–/– mice. Levels of T‐cell‐dependent antirat antibodies [immunoglobulin G (IgG)2a and IgG3] in sera of [OP]–/– mice were significantly lower than that of control mice 2 weeks post‐rat skin grafting. The proliferative responses to xenogeneic rats not to allogeneic mouse stimulation of T cells from [OP]–/– mice were significantly lower than that of wild‐type mice. However, neutrilization of M‐CSF by anti‐M‐CSF monoclonal antibody (mAb) or the addition of M‐CSF to the in vitro culture systems of wild‐type or [OP]–/– mouse T‐responder cells, respectively, did not significantly change proliferative responses and cytolytic function against xenogeneic rat targets of wild‐type or [OP]–/– mouse T‐responder cells. Conclusions: The in vitro data indicate that M‐CSF does not directly regulate cellular immune responses to xenoantigens. The present studies indicate that macrophages may play an important role in immune rejection of xenografts. The precise role of macrophages in xenograft rejection should be further investigated.