Proteome analysis identified human neutrophil membrane tubulovesicular extensions (cytonemes, membrane tethers) as bactericide trafficking

Membrane tubulovesicular extensions (cytonemes)

“…High-performance liquid chromatography and mass spectrometry investigations indicated that TVE disruption released (a) the granular bactericides lactoferrin, lipocalin, myeloperoxidase, cathepsin G and defensins HNP 1-3, (b) energy metabolism enzymes, such as transketolase, glucose-6-phosphate dehydrogenase and glycolytic enzymes phosphoglucose isomerase, enolase, GAPDH and hexokinase II, (c) the actin cytoskeleton proteins moesin, L-plastin, β-and γ-actin, (d) S100A8, S100A9, S100A8/ A9, S100A12 proteins and (e) other proteins, such as glutathione transferase, annexin 1 and ov-serpin. 29 The presence of specific and primary granular bactericides including lactoferrin, lipocalin, mieloperoxidase, cathepsin G and defensins HNP 1-3 in neutrophil TVEs confirmed the hypothesis that TVEs represent protrusions of neutrophil secretory bactericide trafficking. 29 The abundant occurrence of glycolytic enzymes, actin cytoskeletal proteins, annexin1 and S100 proteins in TVEs might be required to execute TVEs fusion with the neutrophil plasma membrane.…”

“…29 The presence of specific and primary granular bactericides including lactoferrin, lipocalin, mieloperoxidase, cathepsin G and defensins HNP 1-3 in neutrophil TVEs confirmed the hypothesis that TVEs represent protrusions of neutrophil secretory bactericide trafficking. 29 The abundant occurrence of glycolytic enzymes, actin cytoskeletal proteins, annexin1 and S100 proteins in TVEs might be required to execute TVEs fusion with the neutrophil plasma membrane. The role of glycolytic enzymes and the actin cytoskeleton in membrane fusion and TVE formation was discussed above.…”

“…102,104,106 Our data revealed NO as an inducer of TVE formation in neutrophils. 26,27,29 We propose that NO regulates neutrophil adhesive interactions via the formation of long and dynamic TVEs, which attach neutrophils to the endothelium in a long-range selectindependent manner. 26,36 In this case the role of integrins, which are located on the cell bodies, in neutrophil adhesion is reduced.…”

“…27 The extracellular binding of bacteria via TVEs containing primary and specific granule bactericides and the subsequent killing of bound bacteria through bactericides released from TVEs upon lysis represents a novel mechanism for eliminating bacteria via neutrophils. 29 This mechanism could share some of the advantages of phagocytosis. The micrometer-long TVEs greatly widen the area, where bacteria are subjected to neutrophilic attack.…”

“…Extracellular binding of bacteria by neutrophil TVEs represents an alternative phagocytotic mechanism to bind and kill pathogens. [26][27][28][29] Notably, there are principle differences between TVEs and so-called "neutrophil extracellular traps," or NETs. According to Zychlinsky and colleagues, neutrophils exposed to uncoated coverslips in the presence of phorbol ether for 4-6 h "extrude" chromatin and granule proteins that form NETs for binding and killing pathogens.…”