Piecemeal degranulation from eosinophils. (A) Piecemeal release of crystalloid granules with a “hollowed out” appearance, shown by electron microscopic analysis of human cultured eosinophils. Arrows show lucent vesicles budding into granule interior, suggestive of vesicular trafficking to and from crystalloid granules. Reprinted from Am J Pathol. 1991;138:69-82 with permission from the American Society for Investigative Pathology.56 (B) Time course of IFNγ-induced CCL5/RANTES release (green) by piecemeal degranulation from major basic protein-positive crystalloid granules (red) in eosinophils. This research was originally published in Blood.57 Copyright The American Society of Hematology. (C) Immunogold labeling of IL-4 (arrowheads) present in small vesicles budding from a crystalloid granule (Gr), indicating piecemeal degranulation as a pathway for cytokine release. Reproduced with permission from Spencer et al.58 (Cytokine receptor-mediated trafficking performed IL-4 in eosinophils identifies an innate immune mechanism of cytokine secretion. Proc Natl Acad Sci U S A. 2006;103(9):3333-3338. Copyright 2006 National Academy of Sciences, USA.) (D) Meshed model of an eosinophil granule with small vesicles budding from it, using contours generated by automated electron tomography. A protrusion can be seen progressively emerging from the granule, in blue (arrowheads). In the center panel, a vesicle is shown in yellow to indicate the way in which vesicles dissociate from the granule. In the right panel, the arrow indicates the same vesicle from a different perspective near the granule (Gr). This model was generated by meshes of contours arising from serial sections of the same granule in a single cell. Cells were fixed and processed for conventional transmission electron microscopy after stimulation with eotaxin. Images were reproduced from Melo et al.59 Reprinted with permission from Traffic. 2005;6:1047-1057, published by John Wiley and Sons.