Assessing neutrophil viability after atypical antipsychotic exposure using cell line PLB-985

Neutrophils comprise 60-70% of an individual's white blood cells and are an essential part of our innate immune systems. Neutrophils act as first-responders to sites of injury or potential infection, where they help to initiate inflammatory responses and/or aid in destruction of an infectious agent. (Witko-Sarsat, 2000)
Atypical antipsychotics, a class of drug commonly used to treat disorders like schizophrenia and insomnia, are known to cause neutropenia and agranulocytosis (a depletion of circulating neutrophils) as a rare, but severe, side effect. (Hong & Wong, 2001) However, the mechanism(s) by which these drugs induce neutropenia is still in question.
In this study, we used the neutrophil model cell line, PLB-985, to assess the effects of four atypical antipsychotics (clozapine, olanzapine, aripiprazole and quetiapine) on cell viability using a plate-based, colorimetric bioassay.
After collecting this initial data, we hypothesize that the reduction in cell viability seen after 48-hour exposure to 20μM and 50μM concentrations of aripiprazole is due to its unique mechanism of action as a partial dopamine agonist. Therefore, we seek to determine if we can both rescue the reduction of cell viability by introducing dopamine antagonists, as well as replicate the phenotype by exposing cells to dopamine hydroch
Download pdf
Abstract/Description: Neutrophils comprise 60-70% of an individual's white blood cells and are an essential part of our innate immune systems. Neutrophils act as first-responders to sites of injury or potential infection, where they help to initiate inflammatory responses and/or aid in destruction of an infectious agent. (Witko-Sarsat, 2000) Atypical antipsychotics, a class of drug commonly used to treat disorders like schizophrenia and insomnia, are known to cause neutropenia and agranulocytosis (a depletion of circulating neutrophils) as a rare, but severe, side effect. (Hong & Wong, 2001) However, the mechanism(s) by which these drugs induce neutropenia is still in question. In this study, we used the neutrophil model cell line, PLB-985, to assess the effects of four atypical antipsychotics (clozapine, olanzapine, aripiprazole and quetiapine) on cell viability using a plate-based, colorimetric bioassay. After collecting this initial data, we hypothesize that the reduction in cell viability seen after 48-hour exposure to 20μM and 50μM concentrations of aripiprazole is due to its unique mechanism of action as a partial dopamine agonist. Therefore, we seek to determine if we can both rescue the reduction of cell viability by introducing dopamine antagonists, as well as replicate the phenotype by exposing cells to dopamine hydroch
Subject(s): Dopamine antagonists
Undergraduate Research
Neutrophils
Atypical antipsychotics
Agranulocytosis
Neutropenia