The Antibacterial Activity of DA-22 through Enhancing the Functions of Human Neutrophils

Abstract

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.