Commentary on Classic Article

The review article by Ann M. Dvorak “Ultrastructural Studies of Human Basophils and Mast Cells,” J. Histochem. Cytochem. 53(9) 1043–1070, 2005, was seminal in defining the distinct ultrastructure and physiological roles of mast cells and basophils. Due to similarities in their structure and function, mast cells were often confused with basophils, and it had also been suggested that mast cells arise from basophils. In this article, using primarily ultrastructural methods, Dvorak examines five criteria—identity, secretion, vesicles, recovery, and synthesis—to elucidate the similarities and differences between these two cell types and confirm their identity as two distinct cell types. In each section, Dvorak reviews the current knowledge and offers new and insightful perspectives on the topic.

The first section on identity delineates the basic ultrastructural characteristics of the two cell types as well as the unique ultrastructural features that distinguish mast cells from basophils. She also points out the distinct intracellular granule patterns seen in mast cells and basophils. The article then turns its attention to degranulation. Two morphological patterns of degranulation following stimulation, piecemeal degranulation (PMD), and anaphylactic degranulation (AND) are described for mast cells and basophils. PMD is characterized by the presence of partially or completely empty granules and the lack of intergranule fusion or granule fusion with the plasma membrane leading to extrusion of the granule content. In contrast, the hallmarks of AND include granule swelling and matrix alteration, intergranule membrane fusion, which give rise to degranulation channels and pore formation at the plasma membrane, which results in granule matrix extrusion and shedding of cytoplasmic processes and membranes. The type and the kinetics of degranulation is related to the form of activation of the mast cells or basophils. The next section deals with the vesicles that are associated with PMD. Elucidation of the role of vesicles required the development of many new tools and resources. The ability to isolate and culture circulating basophils as well as the development of immunocytochemical techniques for electron microscopy facilitated this investigation. As a result, through direct examination, quantification, and immunolabeling of vesicular cargo, Dvorak demonstrated the involvement of vesicular transport in the secretory process in mast cells and basophils. In contrast to some other granulocytes, mast cells and basophils are not end stage cells but do recover following degranulation. During the recovery period, cytoplasmic granules are reconstituted in a time-dependent manner. Secretory granules and lipid bodies may also play a role in protein synthesis. Analysis of mast cells during the recovery period following degranulation showed increased numbers of granule-associated ribosome-like particles and RNA. A similar association was seen with lipid bodies. Therefore, in mast cells, mRNA sorting to secretory granules could help regulate protein concentration both temporally and spatially.

The findings presented in this review still form a basis for our current understanding of the ultrastructure and secretory processes in mast cells and basophils. The observations detailed in this review as well as the unique ultrastructural methods used in the investigations on mast cells and basophils were critical in the determination of mast cells and basophils as distinct cell types with unique morphological and physiological properties.