Blood-Mediated Inflammatory Reaction (IBMIR) and Prevention of IBMIR

In transplantation, function loss of grafts is primarily observed in the early time of transplantation, mainly by two known responses of the instant blood-mediated inflammatory reaction (IBMIR) and hyperacute rejection (HR) [1]. It was reported that the first few hours have been reported to display the IBMIR after cell infusion of xenoantigenic islets [2]. IBMIR is characteristic of innate inflammatory responses and thrombotic pathway displayed by a serial reaction complement activation, immune cell infiltration, platelet adhesion, and coagulation [3]. IBMIR is frequently coupled with thrombosis and releases inflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), and IL-8. Thrombin fundamentally activates platelets. In addition, thrombin can activate innate immune cells of monocytes and neutrophils. Islets-producing tissue factors mainly cause the IBMIR as a causing factor [2, 4]. Therefore, the thrombosis reaction is prevented by blocking of tissue factors in vitro [3]. The IBMIR is also reported in three different transplantations of allo-, auto-, and xenotransplantation for islets [5], as also caused by incompatible species between thrombotic factors of humans and regulatory molecules of pigs. IBMIR is explained to be not only a response occurred in transplantation of allogeneic and xenogeneic islets, but also a responsive phenomenon to the islets and the highly immunogenic cells surrounded with acinar tissues [5]. However, such hurdles are now resolved by α1,3Gal-T KO animals and transgenic gene manipulation of human genes of CD46/CD55/CD59 complement regulators [6]. Using the genetic engineering technology in the immunological-challenged baboon model, HR- and IBMIR-based phenomena have been prevented by the transgenic islets of pigs. Like the HR, IBMIR can be mitigated by genetically disrupting the α1,3Gal-T gene and by transducing human CD46, CD55, and CD59 complement regulators as transgenic genes, respectively, as the blood mediates inflammatory rejection and the regulators protect the inflammation.