Serine proteases
neutrophil elastase (NE), protease 3 (PR3), cathepsin
G (CatG), and neutrophil serine protease 4 (NSP4) are released by
activated neutrophils swarming around the place of pathogen invasion
to provoke an immune response. However, uncontrolled proteolytic activity
of proteases results in various human diseases, including cardiovascular
diseases, thrombosis, and autoimmunity. In addition, proteases can
be hijacked by several viruses to prime virus-derived surface proteins
and evade immune detection by entering into the host cell. Indeed,
porcine elastase increases the suitability of host cells to be infected
by SARS-CoV-1. We compared the cleavage sites of human NE, PR3, and
CatG as well as porcine-derived trypsin within the amino acid sequence
of the proteolytic sensitive activation loop at the interface of S1/S2
of the spike protein (S protein) of SARS-CoV-1 as well as SARS-CoV-2.
As a result, NE and PR3, but not CatG, hydrolyze the scissile peptide
bond adjacent to the polybasic amino acid sequence of the S1/S2 interface
of SARS-CoV-2, which is distinctive from SARS-CoV-1. These findings
suggest that neutrophil-derived NE and PR3 participate in priming
of the S1/S2 interface during an immune response.
Immunotherapy has been established as an important area in the therapy of malignant diseases. Immunogenicity sufficient for immune recognition and subsequent elimination can be bypassed by tumors through altered and/or reduced expression levels of major histocompatibility complex class I (MHC I) molecules. Natural killer (NK) cells can eliminate tumor cells in a MHC I antigen presentation-independent manner by an array of activating and inhibitory receptors, which are promising candidates for immunotherapy. Here we summarize the latest findings in recognizing and regulating MHC I molecules that affect NK cell surveillance of glioblastoma cells.
During inflammation neutrophils become activated and segregate neutrophil serine proteases (NSPs) to the surrounding environment in order to support a natural immune defense. However, an excess of proteolytic activity of NSPs can cause many complications, such as cardiovascular diseases and chronic inflammatory disorders, which will be elucidated on a biochemical and immunological level. The application of selective serine protease inhibitors is the logical consequence in the management of the indicated comorbidities and will be summarized in this briefing.
Neutrophils, migrating to the site of infection, are able to release serine proteases after being activated. These serine proteases comprise cathepsin G (CatG), neutrophil elastase protease 3 (PR3), and neutrophil serine protease 4 (NSP4). A disadvantage of the uncontrolled proteolytic activity of proteases is the outcome of various human diseases, including cardiovascular diseases, thrombosis, and autoimmune diseases. Activity-based probes (ABPs) are used to determine the proteolytic activity of proteases, containing a set of three essential elements: Warhead, recognition sequence, and the reporter tag for detection of the covalent enzyme activity–based probe complex. Here, we summarize the latest findings of ABP-mediated detection of proteases in both locations intracellularly and on the cell surface of cells, thereby focusing on CatG. Particularly, application of ABPs in regular flow cytometry, imaging flow cytometry, and mass cytometry by time-of-flight (CyTOF) approaches is advantageous when distinguishing between immune cell subsets. ABPs can be included in a vast panel of markers to detect proteolytic activity and determine whether proteases are properly regulated during medication. The use of ABPs as a detection tool opens the possibility to interfere with uncontrolled proteolytic activity of proteases by employing protease inhibitors.
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