A role for vesicles in human basophil secretion

Abstract

The evidence for vesicular transport as a mechanism for secretion by human basophils is reviewed. Initially, direct electron-microscopic inspection of experimentally produced and sequentially biopsied contact allergy skin lesions revealed a unique form of secretion termed piecemeal degranulation, characterized by the slow emptying of secretory granule contents (with retention of empty containers) in the absence of extrusion of entire granules. Budding of small vesicles to/from secretory granules was observed, and cytoplasmic vesicles were abundant. A generalized degranulation model was proposed to unify classical regulated secretion and this new form of secretion. Investigation of the mechanism(s) of secretion from human basophils required the development of numerous tools and resources. Chief among these were: (a) isolation and purification of circulating basophils; (b) identification of specific growth factors to increase the supply of this rare granulocyte; (c) understanding of secretogogue mechanisms and reliable analyses of secreted basophil products; and (d) development of ultrastructural preparations allowing imaging of small vesicles and quantifiable small electron-dense tags for granule materials in small vesicles. Applications of these tools to well-defined models of basophil secretion have established a role for vesicles as a mechanism for effecting secretion of histamine and the Charcot-Leyden crystal protein from activated human basophils.

Evaluation of basophil activation in food allergy: present and future applications

“…Interestingly, these patients do not express high baseline levels of CD63 [39], although they may be more sensitive to degranulation due to specific and non-specific stimuli (W. Shreffler, unpublished observation). This is consistent with so-called piecemeal degranulation, whereby granule contents are partially released by vesicle transport without extrusion of granules [48]. If this is the case, one would predict that the levels of vesicle-associated proteins, such as CD203c, CD13 and CD164 (see above), would be up-regulated at baseline.…”

Ultrastructural morphology of adrenal chromaffin cells indicative of a process of piecemeal degranulation

“…In addition, diminished electron densities and picnotic osmiophilic cores within dilated electron lucent containers, as seen in both A and NA cells, are common findings in basophil and mast cell PMD (Dvorak, 1991;Dvorak et al, 1992). Finally, the cytoplasmic vesicles ob- served near or attached to chromaffin granules are similar to vesicle profiles seen in basophils and mast cells undergoing PMD (Dvorak et al, 1996;Dvorak, 1998b). We believe that all of these features may be expressions of PMD in adrenal chromaffin cells.…”

“…Because secretory granules in PMD do not open to the cell exterior, it has been proposed that the discharge mechanism implies the formation of vesicles that shuttle back and forth between the granules and the plasma membrane (Dvorak et al, 1996;Dvorak, 1998b). Vesicles containing bits of granule contents would bud from the perigranule membrane, move through the cytoplasm, and fuse with the plasma membrane.…”

Chromaffin granules in the rat adrenal medulla release their secretory content in a particulate fashion

“…The ultrastructural criteria for PMD include specific granule and cytoplasmic changes (Dvorak, 1991(Dvorak, , 1998. Both are recognizable in chromaffin cells of the rat medulla.…”

“…Since secretory granules do not open to the cell exterior during the PMD reaction, it has been proposed that the discharge mechanism implies the formation of vesicles that shuttle back and forth between the granules and the plasma membrane (Dvorak et al, 1996;Dvorak, 1998).…”