Activation of Eosinophils and Fibroblasts Assessed by Eosinophil Cationic Protein and Hyaluronan in BAL: Association With Acute Rejection in Lung Transplant Recipients

Abstract

Lung transplantation has become an accepted therapy for end-stage lung disease. Acute rejection of the transplanted hung still remains a major clinical problem since it decreases graft survival. Eosinophil cationic protein (ECP) from activated eosinophils, hyaluronan (HYA) from fibroblasts, and circulating intercellular adhesion molecule 1 (1CAM-1) have been associated with acute rejection in kidney and liver grafts. We investigated whether these, as well as other molecules, were increased in acute rejection of lung allografts. Serum and BAL fluid from 38 bronchoscopies performed in 9 single lung, 2 bilateral lung, and 4 heart-lung transplant patients were studied. Differential cell counts were made from the BAL fluid. Levels of ECP, myeloperoxidase (MPO), and HYA were used as indirect markers for activation of eosinophils, neutrophils, and fibroblasts, respectively. In addition, levels of circulating ICAM-1, cVCAM-1, and cE-selectin were analyzed. Twenty-two episodes with acute rejection were diagnosed. Of these, 7 were minimal, 13 were mild, and 2 were of moderate character. We found increased levels of ECP and HYA in BAL fluid during mild acute rejection of the allograft. Numbers of eosinophils were also increased. Activation of neutrophils or neutrophil numbers were not significantly increased. Levels of circulating ICAM-1, cVCAM-1, and cE-selectin did not differ between the groups. This retrospective study shows that measurements of ECP and HYA can give information about the inflammatory process present during acute rejection in patients who have undergone lung transplants. Analysis of cCAMS, however, appears to be of limited value as markers for acute rejection.