Target type: biologicalprocess
Any process that increases the frequency, rate or extent of the directed killing of a gram-negative bacterium by a neutrophil. [GOC:add, GOC:mah]
Positive regulation of neutrophil mediated killing of gram-negative bacteria is a complex process that involves a cascade of molecular events. It begins with the recognition of gram-negative bacteria by neutrophils through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs), which recognize specific pathogen-associated molecular patterns (PAMPs) on the bacterial surface. TLR4, for example, binds to lipopolysaccharide (LPS), a major component of the outer membrane of gram-negative bacteria. This recognition triggers a signaling cascade that leads to the activation of various transcription factors, such as NF-κB, which upregulate the expression of genes encoding antimicrobial proteins and cytokines. Neutrophils then release these antimicrobial agents, including reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, and antimicrobial peptides, such as defensins, into the surrounding environment to kill the bacteria. These molecules are highly effective against gram-negative bacteria, causing damage to their cell membranes and disrupting essential metabolic processes. In addition to these direct killing mechanisms, neutrophils can also trap and engulf bacteria through phagocytosis. Phagocytosis is facilitated by opsonization, where antibodies or complement proteins bind to the bacteria and facilitate their recognition and engulfment by neutrophils. Once the bacteria are internalized, they are enclosed within phagosomes, which fuse with lysosomes containing enzymes and other antimicrobial agents that destroy the bacteria. The activation of neutrophils is also tightly regulated to prevent excessive inflammation and tissue damage. Suppressor molecules, such as IL-10 and TGF-β, can limit the duration and magnitude of the inflammatory response. Furthermore, neutrophils undergo apoptosis after they have cleared the infection, preventing their uncontrolled activation and potential tissue damage.'
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Protein | Definition | Taxonomy |
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Proteinase-activated receptor 2 | A proteinase-activated receptor 2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P55085] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
triptolide | diterpenoid; epoxide; gamma-lactam; organic heteroheptacyclic compound | antispermatogenic agent; plant metabolite | |
seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide | seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide: a proteinase-activated receptor-2-activating peptide; SL-NH2 is NOT Ser-Leu-NH2 here | ||
2-furoyl-ligrlo-amide | 2-furoyl-LIGRLO-amide: a potent and selective proteinase-activated receptor 2 agonist | ||
AZ3451 | benzimidazoles; benzodioxoles; nitrile; organobromine compound; secondary carboxamide | anti-inflammatory agent; autophagy inducer; PAR2 negative allosteric modulator |