Splenic macrophage polarization and plasma lipid remodeling in cardiac allograft rejection

Cardiac transplantation is the final therapeutic option for end-stage heart disease. Immune rejection is one of the major sources of morbidity and mortality. Macrophages play important roles in host defense and immune regulation, yet they remain poorly studied in heart transplant rejection. This study investigated macrophage polarization and associated lipid alterations in a well-established rat model of heart transplant. Splenic macrophage phenotypes, reactive oxygen species (ROS), and lipid peroxide were examined using flow cytometry. Plasma lipids were analyzed by liquid chromatography-mass spectrometry (LC-MS). Next-generation sequencing of mRNA (RNA-seq) was used to analyze the expression of splenic CD11b+ cells genes. Allogeneic heart transplant was associated with systemic innate immune alterations and splenic macrophage M1 polarization. ROS and lipid peroxide levels in splenic CD11b+ cells tended to be higher in allografts than in isografts, although these differences were not statistically significant. Splenic CD11b+ cells showed up-regulation of Nos2, Cxcl10, Cd68, Il1r1, Cenpf, and Cyp27a1 mRNA in allografts compared with isografts, while Insig1 was down-regulated. Plasma CE, LPC, LPE, PC, and SM were decreased in allografts. Splenic macrophage polarization toward the M1 phenotype and plasma lipid remodeling were both observed in allograft rejection, but a causal relationship was not established.