Decreased Expression of Eosinophil Peroxidase and Major Basic Protein Messenger RNAs During Eosinophil Maturation

PURIFICATION of eosinophils from patients with eosinophilia has led to identification of eosinophil subpopulations differing by their cell density.1,2Hypodense eosinophils can be distinguished from normodense eosinophils by impaired oxidative metabolism,3 increased cytotoxic function against parasite targets,4 and increased expression of various membrane receptors.5-7 All these biologic properties involve newly or preformed eosinophil mediators such as lipid mediators (LTC4, PAF-acether) or cationic proteins (eosinophil peroxidase, major basic protein, eosinophil-cationic protein, eosinophil-derived neurotoxin; EPO, MBP, ECP, and EDN, respectively). The biochemical and functional properties of these proteins have been well studied. MBP is a 14-Kd protein8 which is toxic to helminth parasites, tumor cells, and host cells.9 MBP has no recognized enzymatic activity. EPO, so called for its peroxidase activity, consists of two polypeptides of 15 and 55 Kd10and is toxic to parasites,11,12bacteria,13 and tumor or host cells.14 ECP and EDN are proteins of 18- to 21-Kd that share sequence similarity and ribonuclease activity.15 They have been implicated in causing cell dam-age16'17and in neurotoxicity.18 These proteins can be detected in many tissues and biologic fluids.9 Their release has been observed after activation with various stimuli such as interleukins or immunoglobulins.19 After immunoglobulin-dependent activation, preferential release of EPO and MBP under IgE stimulation, in contrast to release of ECP under IgG activation, has allowed us to suggest a selectivity in mediator release.20 Whereas many studies have examined the biologic and biochemical properties of these cationic proteins, considered as preformed proteins, very few reports have studied their synthesis by eosinophils. In this regard, cloning of the various cDNAs encoding cationic proteins21-26 and discovery of the potentiality of cord blood cells (CBC) to differentiate into eosinophils in the presence of interleukins27-29 have recently provided useful tools to approach this question. © 1992 by The American Society of Hematology.