The developmental and biochemical relationships of human basophils and eosinophils and their functional interactions in allergic, parasitic, inflammatory and other diseases are unclear. Basophils and eosinophils may differentiate from a common progenitor, and certain presumably eosinophil specific membrane and cationic granule proteins have been found to be constituents of basophils, but not of neutrophils or mast cells. Some of these eosinophil granule-derived cationic proteins stimulate basophils and mast cells to release mediators of inflammation. To further elucidate interrelated aspects of the ontogeny, biochemistry, and function of human basophilic and eosinophilic leukocytes, the research will study: 1) the comparative localization, and physicochemical and biochemical properties of proteins common to these granulocytes, 2) the comparative biosynthesis, post-translational processing, and/or uptake of these proteins by mature peripheral blood-derived cells and immature cells during differentiation, and 3) the comparative mechanisms for cell activation and extracellular secretion of their common proteins. These studies will use basophils and eosinophils purified both from peripheral blood or from specifically induced cultures of human fetal cord blood mononuclear cells, homogeneously purified eosinophil and basophil proteins, and monospecific antisera to these proteins. Studies of the subcellular localization, enzymatic activity, uptake and secretion of Charcot-Leyden crystal protein (lysophospholipase), eosinophil granule major basic protein and eosinophil peroxidase in the basophil will utilize ultrastructural cytochemistry and autoradiography, immunoelectron microscopy, and specific radioimmunoassays. The biosynthesis, post-translational processing, and secretion of these proteins will be studied by metabolically labeling them in basophils and eosinophils during in vitro differentiation and maturation in cultures of fetal cord blood mononuclear cells induced to differentiate with basophil or eosinophil selective growth factors. Further, the intracellular activation of eosinophil peroxidase to facilitate its own proteolytic degradation via a hypochlorous acid-, chloramine-dependent mechanism, to generate some of the low Mr cationic proteins present in and secreted from the eosinophil granule will be investigated. These studies aim to provide a more integrated understanding of the myelopoietic, biochemical, and functional relationships of basophils and eosinophils, and to further define their dynamic interactions in the basophil/mast cell-eosinophil axis in allergic and related immunologic responses.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Beth Israel Deaconess Medical Center
United States
Zip Code
Coyle, A J; Ackerman, S J; Burch, R et al. (1995) Human eosinophil-granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation. J Clin Invest 95:1735-40
Newton, D L; Walbridge, S; Mikulski, S M et al. (1994) Toxicity of an antitumor ribonuclease to Purkinje neurons. J Neurosci 14:538-44
Rosenberg, H F; Ackerman, S J; Tenen, D G (1993) Characterization of a distinct binding site for the prokaryotic chaperone, GroEL, on a human granulocyte ribonuclease. J Biol Chem 268:4499-503
Ackerman, S J; Corrette, S E; Rosenberg, H F et al. (1993) Molecular cloning and characterization of human eosinophil Charcot-Leyden crystal protein (lysophospholipase). Similarities to IgE binding proteins and the S-type animal lectin superfamily. J Immunol 150:456-68
Uchida, D A; Ackerman, S J; Coyle, A J et al. (1993) The effect of human eosinophil granule major basic protein on airway responsiveness in the rat in vivo. A comparison with polycations. Am Rev Respir Dis 147:982-8
Coyle, A J; Ackerman, S J; Irvin, C G (1993) Cationic proteins induce airway hyperresponsiveness dependent on charge interactions. Am Rev Respir Dis 147:896-900
Zon, L I; Yamaguchi, Y; Yee, K et al. (1993) Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription. Blood 81:3234-41
Dvorak, A M; Ackerman, S J; Furitsu, T et al. (1992) Mature eosinophils stimulated to develop in human-cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. II. Vesicular transport of specific granule matrix peroxidase, a mechanism for effecting piecemeal degranulation. Am J Pathol 140:795-807
Zhou, Z; Tenen, D G; Dvorak, A M et al. (1992) The gene for human eosinophil Charcot-Leyden crystal protein directs expression of lysophospholipase activity and spontaneous crystallization in transiently transfected COS cells. J Leukoc Biol 52:588-95
Golightly, L M; Thomas, L L; Dvorak, A M et al. (1992) Charcot-Leyden crystal protein in the degranulation and recovery of activated basophils. J Leukoc Biol 51:386-92

Showing the most recent 10 out of 26 publications