Biology subjects

Jamieson, A. M.

Publications and source records attributed to Jamieson, A. M..

4 recordsLinked to original sources

bioRxiv2024

Peripheral CaV2.2 channels in skin regulate prolonged heat hypersensitivity during neuroinflammation

Neuroinflammation can lead to chronic maladaptive pain affecting millions of people worldwide. Neurotransmitters, cytokines, and ion channels are implicated in neuro-immune cell signaling but their roles in specific behavioral responses are not fully elucidated. Voltage-gated CaV2.2 channel activity in skin controls rapid and transient heat hypersensitivity induced by intradermal capsaicin via IL-1 cytokine signaling. CaV2.2 channels are not, however, involved in mechanical hypersensitivity that developed in the same animal model. Here, we show that CaV2.2 channels are also critical for heat hypersensitivity induced by the intradermal (id) Complete Freunds Adjuvant (CFA) model of chronic neuroinflammation that involves ongoing cytokine signaling for days. Ongoing CFA-induced cytokine signaling cascades in skin lead to pronounced edema, and hypersensitivity to sensory stimuli. Peripheral CaV2.2 channel activity in skin is required for the full development and week-long time course of heat hypersensitivity induced by id CFA. CaV2.2 channels, by contrast, are not involved in paw edema and mechanical hypersensitivity. CFA induced increases in cytokines in hind paws including IL-6 which was dependent on CaV2.2 channel activity. Using IL-6 specific neutralizing antibodies, we show that IL-6 contributes to heat hypersensitivity and, neutralizing both IL-1 and IL-6 was even more effective at reducing the magnitude and duration of CFA-induced heat hypersensitivity. Our findings demonstrate a functional link between CaV2.2 channel activity and the release of IL-6 in skin and show that CaV2.2 channels have a privileged role in the induction and maintenance of heat hypersensitivity during chronic forms of neuroinflammation in skin. Significance StatementNeuroinflammation can lead to chronic maladaptive pain. Neurotransmitters, ion channels, cytokines, and cytokine receptors are implicated in neuron-immune signaling, but their importance in mediating specific behavioral responses are not fully elucidated. We show that the activity of peripheral CaV2.2 calcium ion channels in skin play a unique role in the induction and maintenance of heat hypersensitivity in the CFA model of prolonged neuroinflammation, without accompanying effects on edema and mechanical hypersensitivity. Blocking peripheral CaV2.2 channel activity reduces local cytokine levels in hind paws injected with CFA including IL-6 and neutralizing IL-6 reduces CFA- induced heat hypersensitivity. Our studies define key signaling molecules that act locally in skin to trigger and maintain heat hypersensitivity during chronic neuroinflammation.

neuroscience↗

bioRxiv2021

Graphene oxide/silver nanoparticle ink formulations rapidly inhibit influenza A virus and OC43 coronavirus infection in vitro

Respiratory tract infections present a significant risk to the human population, both through seasonal circulation and novel introductions with pandemic potential. There is a strong need for antiviral compounds with broad antimicrobial activity that can be coated onto filtration systems and personal protective equipment to augment their ability to remove infectious particles from the environment. Graphene oxide and silver nanoparticles are both materials with documented antimicrobial properties. Here, we tested the in vitro antiviral properties of several graphene oxide-silver nanoparticle composite materials, which were prepared through three different methods: reduction with silver salt, direct addition of silver nanospheres, and direct addition of silver nanospheres to thiolized graphene. These materials were tested over short time scales for their antiviral activity against two enveloped RNA viruses, influenza A virus and OC43 coronavirus, by performing viral plaque assays after exposure of the viruses to each material. It was found that the graphene oxide - silver nanoparticle materials generated by direct addition of the silver nanospheres were able to completely inhibit plaque formation by both viruses within one minute of exposure. Materials generated by the other two methods had varying levels of efficacy against influenza A virus. These studies indicate that graphene oxide-silver nanoparticle composite materials can rapidly neutralize RNA viruses and demonstrate their potential for use in a wide range of applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/432893v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@7940d4org.highwire.dtl.DTLVardef@8f3207org.highwire.dtl.DTLVardef@11d9c1eorg.highwire.dtl.DTLVardef@f489a2_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2020

Unique transcriptional changes in coagulation cascade genes in SARS-CoV-2-infected lung epithelial cells: A potential factor in COVID-19 coagulopathies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. In addition to the acute pulmonary symptoms of COVID-19 (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. Currently, the molecular pathogenesis underlying COVID-19 associated coagulopathies are unknown. While there are many theories for the cause of this pathology, including hyper inflammation and excess tissue damage, the cellular and molecular underpinnings are not yet clear. By analyzing transcriptomic data sets from experimental and clinical research teams, we determined that changes in the gene expression of genes important in the extrinsic coagulation cascade in the lung epithelium may be important triggers for COVID-19 coagulopathy. This regulation of the extrinsic blood coagulation cascade is not seen with influenza A virus (IAV)-infected NHBEs suggesting that the lung epithelial derived coagulopathies are specific to SARS-Cov-2 infection. This study is the first to identify potential lung epithelial cell derived factors contributing to COVID-19 associated coagulopathy. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/182972v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@93cfb7org.highwire.dtl.DTLVardef@2a23c9org.highwire.dtl.DTLVardef@93623borg.highwire.dtl.DTLVardef@161e25_HPS_FORMAT_FIGEXP M_FIG C_FIG AUTHOR SUMMARYO_ST_ABSWhy was this study done?C_ST_ABSO_LISevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. C_LIO_LIIn addition to the acute pulmonary symptoms of COVID-19 (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. C_LIO_LICurrently, the molecular pathogenesis underlying COVID-19 associated coagulopathies are unknown. Understanding the molecular basis of dysregulated blood coagulation during SARS-CoV-2 infection may help promote new therapeutic strategies to mitigate these complications in COVID-19 patients. C_LI What did the researchers do and find?O_LIWe analyzed three publicly available RNA sequencing datasets to identify possible molecular etiologies of COVID-19 associated coagulopathies. These data sets include sequencing libraries from clinically isolated samples of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMCs) from SARS-CoV-2 positive patients and healthy controls. We also analyzed a publicly available RNA sequencing dataset derived from in vitro SARS-CoV-2 infected primary normal human bronchial epithelial (NHBE) cells and mock infected samples. C_LIO_LIPathway analysis of both NHBE and BALF differential gene expression gene sets. We found that SARS-CoV-2 infection induces the activation of the extrinsic blood coagulation cascade and suppression of the plasminogen activation system in both NHBEs and cells isolated from the BALF. PBMCs did not differentially express genes regulating blood coagulation. C_LIO_LIComparison with influenza A virus (IAV)-infected NHBEs revealed that the regulation of the extrinsic blood coagulation cascade is unique to SARS-CoV-2, and not seen with IAV infection. C_LI What do these findings mean?O_LIThe hyper-activation of the extrinsic blood coagulation cascade and the suppression of the plasminogen activation system in SARS-CoV-2 infected epithelial cells may drive diverse coagulopathies in the lung and distal organ systems. C_LIO_LIThe gene transcription pattern in SARS-CoV-2 infected epithelial cells is distinct from IAV infected epithelial cells with regards to the regulation of blood coagulation. C_LI

pathology↗

bioRxiv2020

Pulmonary infection interrupts acute cutaneous wound healing through disruption of chemokine signals

Studies of the immune response typically focus on single-insult systems, with little known about how multi-insult encounters are managed. Pneumonia in patients recovering from surgery is a clinical situation that exemplifies the need for the patient to mount two distinct immune responses. Examining this, we have determined that poor wound healing is an unreported complication of pneumonia in laparotomy patients. Using mouse models, we found that lung infection suppressed the trafficking of innate leukocytes to wounded skin, while pulmonary resistance to the bacterial infection was maintained. The dual insults caused distinct systemic and local changes to the inflammatory response, the most striking being a rapid and sustained decrease in chemokine levels at the wound site of mice with pneumonia. Remarkably, replenishing wound chemokine levels completely rescued the wound-healing rate in mice with a pulmonary infection. These findings have broad implications for understanding the mechanisms guiding the innate immune system to prioritize inflammatory sites. One Sentence SummaryChemokine-mediated signaling drives the prioritization of innate immune responses to bacterial pulmonary infection over cutaneous wound healing. HighlightsO_LIHuman laparotomy patients with pneumonia have an increased rate of incision dehiscence, and this observation can be recapitulated in mouse models of bacterial lung infections and skin wounds. C_LIO_LILung infection causes rapid and sustained suppression of skin wound chemokine and inflammatory cytokine production as well as leukocyte recruitment. C_LIO_LIUnique systemic shifts in the immune compartment occur with two inflammatory insults, including the cytokine/chemokine signature and the mobilization, recruitment, and phenotype of innate leukocytes. C_LIO_LIRestoration of chemokine signaling in the wounds of mice that have a lung infection results in increased neutrophil trafficking to the wound site and rescues the rate of healing. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/084442v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@861000org.highwire.dtl.DTLVardef@1847251org.highwire.dtl.DTLVardef@6d6438org.highwire.dtl.DTLVardef@1ce99c6_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗