Monocyte derived macrophages from lung transplantation patients have an increased M2 profile

Abstract

Introduction: Lung transplantation (LTx) is a last treatment option for patients with an end-stage pulmonary disease. Although the monocyte-macrophage lineage is accepted to be clinically important only little is known about the effect of immunosuppressive drugs in combination with chronic rejection. It is likely that local inflammatory conditions and immunosuppressive medication alter the activation state of macrophages. The goal of this study was to determine how monocyte derived macrophage subsets were affected in LTx patients. Methods: PBMC's were obtained by ficoll density gradient centrifugation and cultured in RPMI with 10% FCS for 7 days. For identification and quantification of cultured monocyte derived macrophages fluorescence-activated cell sorting analysis was performed. Markers including; CD16, CD64, CD200r, CD163 and CD14 were used to determine M1, M2a and M2b macrophages. Results: Transplantation patients showed an increased and frequency (p = 0.0245) for M2a macrophages compared to healthy controls. Also, median fluorescence intensity of CD163, CD64, HLA-DR and CD200r increased with transplantation. Discussion: An increase in M2 phenotype macrophages in transplantation patients is in line with the latest findings in solid organ transplantation. M2 macrophages are associated with tissue-regeneration and diminished capacity of host defence, possibly leading to fibrosis development [1]. What this exactly means for the disease process and current clinical assessment requires further investigation. Keywords: Lung transplantation, Chronic lung allograft dysfunction, Monocyte-derived macrophages