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Review
. 2023 May 4;24(9):8257.
doi: 10.3390/ijms24098257.

Multiple Shades of Gray-Macrophages in Acute Allograft Rejection

Katharina Lackner  1 , Susanne Ebner  1 , Katrin Watschinger  2 , Manuel Maglione  1   3
Affiliations
Review

Multiple Shades of Gray-Macrophages in Acute Allograft Rejection

Katharina Lackner et al. Int J Mol Sci. .

Abstract

Long-term results following solid organ transplantation do not mirror the excellent short-term results achieved in recent decades. It is therefore clear that current immunosuppressive maintenance protocols primarily addressing the adaptive immune system no longer meet the required clinical need. Identification of novel targets addressing this shortcoming is urgently needed. There is a growing interest in better understanding the role of the innate immune system in this context. In this review, we focus on macrophages, which are known to prominently infiltrate allografts and, during allograft rejection, to be involved in the surge of the adaptive immune response by expression of pro-inflammatory cytokines and direct cytotoxicity. However, this active participation is janus-faced and unspecific targeting of macrophages may not consider the different subtypes involved. Under this premise, we give an overview on macrophages, including their origins, plasticity, and important markers. We then briefly describe their role in acute allograft rejection, which ranges from sustaining injury to promoting tolerance, as well as the impact of maintenance immunosuppressants on macrophages. Finally, we discuss the observed immunosuppressive role of the vitamin-like compound tetrahydrobiopterin and the recent findings that suggest the innate immune system, particularly macrophages, as its target.

Keywords: acute rejection; alkylglycerol monooxygenase; immunosuppression; macrophages; polarization; tetrahydrobiopterin; transplantation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunosuppressive effect of BH4 in transplantation. (a) NOSs are identified as treatment targets for BH4-related immunosuppression in ischemia reperfusion injury and chronic rejection while NOS could be excluded as target for acute rejection. (b) Due to its upregulation in M2 macrophages that are linked with enhanced lipolysis, FAO and OXPHOS, AGMO might be the target for BH4-related immunosuppression in acute rejection.
See this image and copyright information in PMC

References

    1. Guo Z., Zhao Q., Jia Z., Huang C., Wang D., Ju W., Zhang J., Yang L., Huang S., Chen M., et al. A Randomized-Controlled Trial of Ischemia-Free Liver Transplantation for End-Stage Liver Disease. J. Hepatol. 2023 doi: 10.1016/j.jhep.2023.04.010. - DOI - PubMed
    1. Nasralla D., Coussios C.C., Mergental H., Akhtar M.Z., Butler A.J., Ceresa C.D.L., Chiocchia V., Dutton S.J., García-Valdecasas J.C., Heaton N., et al. A Randomized Trial of Normothermic Preservation in Liver Transplantation. Nature. 2018;557:50–56. doi: 10.1038/s41586-018-0047-9. - DOI - PubMed
    1. Kumar L., Sahu S., Deo A.S., Selvakumar R., Panchwag A.A., Pavithran P. Recent Advances in Anaesthesia for Abdominal Solid Organ Transplantation. Indian J. Anaesth. 2023;67:32–38. doi: 10.4103/ija.ija_1025_22. - DOI - PMC - PubMed
    1. Chan S., Ng S., Chan H.P., Pascoe E.M., Playford E.G., Wong G., Chapman J.R., Lim W.H., Francis R.S., Isbel N.M., et al. Perioperative Antibiotics for Preventing Post-Surgical Site Infections in Solid Organ Transplant Recipients. Cochrane Database Syst. Rev. 2020;8:CD013209. doi: 10.1002/14651858.CD013209. - DOI - PMC - PubMed
    1. Calne R.Y., Rolles K., Thiru S., Mcmaster P., Craddock G.N., Aziz S., White D.J.G., Evans D.B., Dunn D.C., Henderson R.G., et al. Cyclosporin a Initially as the Only Immunosuppressant in 34 Recipients of Cadaveric Organs: 32 Kidneys, 2 Pancreases, and 2 Livers. Lancet. 1979;314:1033–1036. doi: 10.1016/S0140-6736(79)92440-1. - DOI - PubMed