Thesis
The Therapeutic Potential of DX23 in Elevating Neutrophil Antimicrobial Defense
Neutrophils play an important role in the innate immune mechanism. During pathogen
encounter, these cells gather at the infection site and perform various functions. Neutrophil could
effectively eliminate pathogens by performing their functions such as respiratory burst,
degranulation, phagocytosis, and formation of neutrophil extracellular traps (NETs). Therefore,
neutrophil activation emerges as a crucial role in protecting the host from pathogen infection.
Aiming neutrophils for therapeutic strategies has been a serious attempt due to the complex
signaling mechanisms and pathways. The investigation for potential drugs that ameliorate
neutrophil function remains unclear. DX23 is one of the clinical drug compound candidates that is
tested for screening activity towards neutrophil. This research would like to address the potential
of DX23 as one of the drug candidates tested for enhancing neutrophil in maximizing their
capability in regulating antimicrobial activity. The experimental design for this research utilizes
immunofluorescence staining, flow cytometry, and calcium mobilization assay in order to
elucidate the molecular mechanisms underlying the responses of neutrophils and its pathway.
The result showed that DX23 is able to stimulate the formation of NETs web in capturing
bioparticles, and could also induce the expression of CD11b and CD18 integrin surface markers.
Furthermore, the calcium mobilization assay showed that DX23 could induce intracellular calcium
mobilization in human neutrophils in a calcium-free and calcium-containing system. This
concludes that DX23 is able to stimulate antibacterial activities in human neutrophil. Moreover,
this research may lay foundations in generating innovative therapeutic strategies that target the
neutrophil in dealing with diverse clinical conditions, which may boost the patient's health
conditions
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