Opioids are typically
used for the treatment of pain related to
disease or surgery. In the body, they enter the bloodstream and interact
with a variety of immune and neurological cells that express the μ-,
δ-, and κ-opioid receptors. One blood-borne cell-like
body that is not well understood in the context of opioid interactions
is the platelet. The platelet is a highly sensitive anucleate cell-like
fragment responsible for maintaining hemostasis through shape change
and the secretion of chemical messengers. This research characterizes
platelet opioid receptors, how specific receptor agonists impact platelet
exocytosis, and the role of the κ-and μ-receptors in platelet
function. Platelets were found to express all three opioid receptors,
but upon stimulation with their respective agonist no activation was
detected. Furthermore, exposure to the opioid agonists did not impact
traditional platelet secretion stimulated by thrombin, a natural platelet
activator. In addition, data collected from knockout mice suggest
that the opioid agonists may be interacting nonspecifically with platelets.
Dark-field images revealed differences in activated platelet shape
between the κ- and μ-knockout platelets and the control
platelets. Finally, κ-knockout platelets showed variations in
their ability to adhere and aggregate compared to control platelets.
Overall, these data show that platelet function is not likely to be
heavily affected by blood-borne opioids.
Platelets are anuclear circulating cell bodies within the bloodstream commonly known for their roles in clot formation during vascular injury to prevent blood loss. They also have significant impact in a range of diseases, including malaria. However, the role of platelets in malaria is controversial, with contradicting evidence suggesting either that they assist in destruction of malarial parasites or facilitate a severe form of malaria. Precedent work suggests that the timing of infection is critical in determining whether platelets switch roles from being protective to deleterious. As such, the work herein makes use of the unique mechanistic perspective offered by carbon-fiber microelectrode amperometry (CFMA) to understand how platelet secretion is impacted in malarial infection stages (ascending parasite count versus descending parasite count). Malarial platelet behavior was compared to platelets from noninfected control mice by probing their exocytotic function. Results suggest that mouse malaria caused by the parasite Plasmodium chabaudi, during both ascending and descending infection stages, reduces platelet exocytotic events and delays platelet granule fusion; in addition, platelets are more impacted by the disease early in the infection stages. In all, understanding platelet behavior in the malarial context may present new therapeutic routes to treat or cure malaria.
Mast
cells (MCs) are effector cells of the immune system commonly
known for their role in asthma and allergy. They are present throughout
biological systems in various tissues, serving as an interface between
the biological system and environment. Previous work characterizing
the impact of malaria on MCs revealed contradictory results, showing
minimal to strong correlation between MC degranulation and disease
progression. This work seeks to reveal how MC degranulation is impacted
in the presence of malaria, induced by Plasmodium chabaudi, using a mouse model and a single cell measurement technique that
reveals exquisite biophysical detail about any impacts to the degranulation
process. It was hypothesized that the malaria parasites would impact
MC degranulation response during live infection, and the differences
would be revealed via carbon-fiber microelectrode amperometry. In
fact, the data collected show that different stages of malaria infection
affect MC degranulation differently, affirming the importance of considering
different infection stages in future studies of malarial immune response.
Furthermore, a comparison of MC degranulation response to that measured
from platelets under similar circumstances shows similar trends in
quantitative degranulation, suggesting that MC and platelet exocytosis
machinery are affected similarly despite their distinct biological
roles. However, based on the small number of mouse replicates, the
studies herein suggest that there should be further study about cellular
and disease processes. Overall, the work herein reveals important
details about the role of MCs in malaria progression, relevant during
treatment decisions, as well as a potentially generalizable impact
on chemical messenger secretion from cells during malarial progression.
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