Granule exocytosis contributes to priming and activation of the human neutrophil respiratory burst
SM Uriarte, MJ Rane, GC Luerman… - The Journal of …, 2011 - journals.aai.org
The Journal of Immunology, 2011•journals.aai.org
The role of exocytosis in the human neutrophil respiratory burst was determined using a
fusion protein (TAT–SNAP-23) containing the HIV transactivator of transcription (TAT) cell-
penetrating sequence and the N-terminal SNARE domain of synaptosome-associated
protein-23 (SNAP-23). This agent inhibited stimulated exocytosis of secretory vesicles and
gelatinase and specific granules but not azurophil granules. GST pulldown showed that TAT–
SNAP-23 bound to the combination of vesicle-associated membrane protein-2 and syntaxin …
fusion protein (TAT–SNAP-23) containing the HIV transactivator of transcription (TAT) cell-
penetrating sequence and the N-terminal SNARE domain of synaptosome-associated
protein-23 (SNAP-23). This agent inhibited stimulated exocytosis of secretory vesicles and
gelatinase and specific granules but not azurophil granules. GST pulldown showed that TAT–
SNAP-23 bound to the combination of vesicle-associated membrane protein-2 and syntaxin …
Abstract
The role of exocytosis in the human neutrophil respiratory burst was determined using a fusion protein (TAT–SNAP-23) containing the HIV transactivator of transcription (TAT) cell-penetrating sequence and the N-terminal SNARE domain of synaptosome-associated protein-23 (SNAP-23). This agent inhibited stimulated exocytosis of secretory vesicles and gelatinase and specific granules but not azurophil granules. GST pulldown showed that TAT–SNAP-23 bound to the combination of vesicle-associated membrane protein-2 and syntaxin-4 but not to either individually. TAT–SNAP-23 reduced phagocytosis-stimulated hydrogen peroxide production by 60% without affecting phagocytosis or generation of HOCl within phagosomes. TAT–SNAP-23 had no effect on fMLF-stimulated superoxide release but significantly inhibited priming of this response by TNF-α and platelet-activating factor. Pretreatment with TAT–SNAP-23 inhibited the increase in plasma membrane expression of gp91 phox in TNF-α–primed neutrophils, whereas TNF-α activation of ERK1/2 and p38 MAPK was not affected. The data demonstrate that neutrophil granule exocytosis contributes to phagocytosis-induced respiratory burst activity and plays a critical role in priming of the respiratory burst by increasing expression of membrane components of the NADPH oxidase.
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