Thesis
The Antibacterial Activity of DA-22 through Enhancing the Functions of Human Neutrophils
Neutrophils are a type of white blood cell that act as the first line of the innate immune system to
protect and against invading pathogens from the human body. Generally, neutrophils are the most
abundant cells that play an important role in response to infections through their ability to migrate
into affected tissue upon pathogens invasion. The activation of neutrophils are able to engage in the
immune response against pathogenic bacteria through several mechanisms including, phagocytosis,
degranulation, respiratory burst, neutrophils extracellular traps (NETs) formation, calcium
mobilization, and neutrophils adhesion. DA-22 is a confidential drug, however, DA-22 was
commercialized and sold in the market that might also be applied for the patent in the future. To our
knowledge, there is no previous study that investigates the effectiveness of DA-22 on neutrophil
activation. Hence, this research was conducted to examine the ability of DA-22 in activating human
neutrophils and their antibacterial properties against pathogenic bacteria. The investigation involved
conducting experiments, including assays for elastase release and superoxide generation to assess
degranulation and respiratory burst in neutrophils. Another experiment was also performed,
including NETs, CD marker detection, and intracellular calcium measurement to assess NETs
formation, neutrophil integrin expression, and ER calcium release respectively. The result indicated
that DA-22 significantly induced elastase release, integrin expression, and NETs formation, but did not
induce respiratory burst and calcium release in human neutrophils. In conclusion, our findings
demonstrated that DA-22 is able to activate neutrophil functions as an antimicrobial activity against
pathogenic bacteria.
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