Macrophages in solid organ transplantation

Abstract

Macrophages are highly plastic hematopoietic cells with diversified functions related to their anatomic location and differentiation states. A number of recent studies have examined the role of macrophages in solid organ transplantation. These studies show that macrophages can induce allograft injury but, conversely, can also promote tissue repair in ischemia-reperfusion injury and acute rejection. Therapeutic strategies that target macrophages to improve outcomes in solid organ transplant recipients are being examined in preclinical and clinical models. In this review, we discuss the role of macrophages in different types of injury and rejection, with a focus on macrophage-mediated tissue injury, specifically vascular injury, repair and remodeling. We also discuss emerging macrophage-centered therapeutic opportunities in solid organ transplantation.

Cyclosporine Does Not Prevent Microvascular Loss in Transplantation but Can Synergize With a Neutrophil Elastase Inhibitor, Elafin, to Maintain Graft Perfusion During Acute Rejection

“…Following transplantation, the graft microvasculature encounters multiple insults including ischemia reperfusion injury and alloimmune attack (8, 32). Despite treatment with powerful immunosuppressants, the graft microvascular circulation sustains repetitive injury followed by inadequate regeneration which eventually leads to prolonged tissue hypoxia and accelerated fibrotic remodeling.…”

Macrophages as Effectors of Acute and Chronic Allograft Injury

“…Activated T cells also recruit a large number of innate cells including macrophages and granulocytes into the allograft where they either directly or indirectly mediate graft failure. Following transplantation, macrophages can also differentiate into many functionally different subsets, mediating phagocytosis of necrotic cells, secretion of pro-inflammatory cytokines, production of reactive oxygen species, as well as mediating tissue repair, regeneration, and immunoregulation [5]. Other innate cells involved in allograft rejection include natural killer (NK) cells.…”

Donor Hepatic Steatosis Induce Exacerbated Ischemia-Reperfusion Injury Through Activation of Innate Immune Response Molecular Pathways

“…Independently of allograft type, macrophages accumulation and activation occur within the early phase of IRI processes triggering quick and intense innate immune response activation and organ injury (42). Moreover, through the production of pro-inflammatory mediator and its capacity as antigen presenting cells, accumulated macrophages may promote adaptive T cell response (18,42).…”

“…Moreover, through the production of pro-inflammatory mediator and its capacity as antigen presenting cells, accumulated macrophages may promote adaptive T cell response (18,42). Previous studies demonstrated increased activity of Kupffer cells (KC), the hepatic macrophage, in steatotic liver allografts (17).…”

“…ROS scavenging mechanisms (superoxide dismutases) represent candidates for therapeutic interventions to minimize oxidative stress (29). However, the TLR4 signaling pathway is essential for macrophage activation, and its deficiency demonstrated protective effects for IRI injury basically involving reduced levels of TNF-α and IL-6 cytokines (42,44,45). In addition, activation of TLR4 signaling induces adaptive response by increasing CD4 cells infiltration constantly sustained as demonstrated in murine models (22).…”