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Enzyme-Releasing Peptide
Published in Jason Kelley, Cytokines of the Lung, 2022
Allen B. Cohen, Edmund J. Miller, Cassandra MacArthur
Neutrophils contain different kinds of granules or packets of enzymes that are released to the extracellular milieu when the granules are extruded (degranulated). Each type of granule contains different enzymes, and each is released by separate kinds of stimuli. Some of the granules are easy to release, and the release of others is difficult. One type of granule, the specific granule, contains receptors on the granule membrane. When the specific granule constituents are extruded, the granule’s membranes become part of the plasma membrane and the receptors become accessible to their agonists or up-regulated. Azurophilic granules are more difficult to release and contain elastase, myeloperoxidase, and other proteinases and hydrolases.
Constitutive Host Resistance
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The granules of the neutrophil and eosinophil contain enzymes, whereas those within the basophil contain biologically active amines. The enzymes in the neutrophilic granules are important for the destruction and digestion of microorganisms and other foreign organic materials (Table 3.1). The granules are classified into two types: the primary or azurophilic granules, and the secondary, or specific, granules. The terms primary and secondary refer to the color or appearance of the granules during differentiation rather than to the importance of the granules. The azurophilic granules contain peroxidase, myeloperoxidase, acid hydrolases, neutral proteases, cationic antimicrobial proteins, and lysozyme. The neutral proteases include elastase, collagenase, and cathepsin G. Enzymes released by neutrophils will activate complement and generate kinins (see chapter 4); the enzymes therefore enhance vascular permeability and chemotaxis indirectly. The specific granules contain lactoferrin and lysozyme.
Phagocytosis By Human Neutrophils
Published in Hans H. Gadebusch, Phagocytes and Cellular Immunity, 2020
The large peak of turbidity (peak III) represents the azurophil granules of the cell.24,267,268 These are generally considered to be true lysosomes and contain a large number of acid hydrolases. In addition to the acid hydrolases typical of most lyso somes, the azurophil granules also contain the myeloperoxidase (MPO) of the cell and about 50% of the lysozyme.M267,268 The remaining lysozyme is found in the specific granules. A number of neutral proteases have been localized to the azurophil granule.272 A series of seven cationic proteins with bactericidal activity has been localized to the azurophil granules in rabbit neutrophils;26 similar proteins have been identified in human neutrophils.273
The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function
Published in Platelets, 2023
Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N. Smith, Harry Chanzu, Ming Zhang, Sidney W. Whiteheart
Compensating roles for VAMPs in granule secretion have been studied in other systems. Zhao et al. showed that V2, V3, and V8 have a major role in GLUT4 trafficking in adipocytes, but V7 does not.26 In chromaffin cells, V2 is the dominant isoform for catecholamine secretion and in its absence, V3 can efficiently compensate.27 In mast cells, the cargoes are packed into distinct subsets of secretory granules, and the release of at least some of these granules is mediated by V8, while V2 and V3 appear not to be important.28 The release of granule cargo from neutrophils is mediated by the SNARE complexes consisting of different VAMPs.29 While V2 mediated release of cargo from tertiary granules, V7 played a role in azurophilic granule release. V1 was found to be crucial for both of these release events. These studies underline the heterogeneous nature of VAMP usage in the secretory granule release from different cell types. Whether this is due to the promiscuous pairing of SNAREs to mediate membrane fusion or represents a pathway to fine-tune release kinetics in a context-specific manner remains to be determined.
A novel 4-dimensional live-cell imaging system to study leukocyte-endothelial dynamics in ANCA-associated vasculitis
Published in Autoimmunity, 2020
Catriona A. Walls, Neil Basu, Gayle Hutcheon, Lars P. Erwig, Mark A. Little, Dana Kidder
Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of devastating autoimmune disorders characterised by relapsing necrotising vasculitis of small blood vessels, commonly involving kidneys and lungs. Considering the aggressive inflammation and multisystem nature of AAV, it is associated with significant morbidity and mortality [1]. The aetiology of AAV is unclear, but genetic and environmental factors, including infections, are proposed in the initiation of autoimmunity through dysfunctional innate and adaptive immune responses [2]. ANCA autoantibodies develop in susceptible individuals and target the antigens myeloperoxidase (MPO) and proteinase 3 (PR3). These antigens are present in the azurophilic granules of neutrophils and lysosomes of monocytes [3].
Synthesis, biological evaluation, and molecular modelling studies of potent human neutrophil elastase (HNE) inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Maria Paola Giovannoni, Igor A. Schepetkin, Mark T. Quinn, Niccolò Cantini, Letizia Crocetti, Gabriella Guerrini, Antonella Iacovone, Paola Paoli, Patrizia Rossi, Gianluca Bartolucci, Marta Menicatti, Claudia Vergelli
Proteases are enzymes implicated in cellular reactions involving the cleavage of protein substrates1. Serine proteases are characterised by the presence of a serine residue at the active site2. They are divided into four classes: chymotrypsin, subtilisin, carboxypeptidase Y, and caseinolytic protease3. Human neutrophil elastase (HNE), proteinase 3 (PR3), cathepsin G, and the recently discovered NSP44 are serine proteases belonging to the chymotrypsin family and represent neutrophil serine proteases (NSP)5,6. NSP are synthesised and expressed in neutrophil azurophilic granules. Neutrophils play a pivotal role in host defence, inflammation and tissue remodelling, and HNE is a key mediator of neutrophil-driven inflammation7.