Regulation of Neutrophil Degranulation and Cytokine Secretion: A Novel Model Approach Based on Linear Fitting

Figure 6

Hypothetical models of fitted cytokines and granules in human neutrophils. (a) Neutrophil-derived cytokines are released in a hierarchical sequence coincident with the roles of granules (IV secretory vesicles, III gelatinase granules, II specific granules, and I azurophil granules) during the microbial elimination processes and inflammatory response. (b) Cytokines and granules are released in a concurrent fashion but could additionally be localized in or mobilized to the different granule types. Classical secretory pathways are mediated through the endoplasmic reticulum (ER) and Golgi complex (IL6 and IL8). IL1β is secreted on a nonconventional pathway. Possible routes for cytokine trafficking (after ER-Golgi or after cleavage) and mobilization to the plasma membrane relative to degranulation are shown in red. Different types of granules are characterized by their CD markers and proteolytic enzymes (triangles): CD63, myeloperoxidase (MPO), and neutrophil elastase (NE) for azurophil granules; CD66b and lactoferrin (LTF) for specific granules; CD11b and matrix metallopeptidase-9 (MMP-9) for gelatinase granules; and CD45 for secretory vesicles. Upon mobilization of the granules to the plasma membrane, granule docking and fusion lead to the translocation of the CD markers to the plasma membrane and the release of proteolytic enzymes.

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