Carbon-Fiber Microelectrode Amperometry Reveals Sickle-Cell-Induced Inflammation and Chronic Morphine Effects on Single Mast Cells
Year: 2012
Type: article
Abstract: Sickle cell disease, caused by a mutation of hemoglobin, is characterized by a complex pathophysiology including an important inflammatory component. Mast cells are tissue-resident leukocytes known to influence a range of immune functions in a variety of different ways, largely through the secretion of biologically active mediators from preformed granules. However, it is not understood how mast cells influence the inflammatory environment in sickle cell disease. A notable consequence of sickle cell disease is severe pain. Therefore, morphine is often used to treat this disease. Because mast cells express opioid receptors, it is pertinent to understand how chronic morphine exposure influences mast cell function and inflammation in sickle cell disease. Herein, carbon-fiber microelectrode amperometry (CFMA) was used to monitor the secretion of immunoactive mediators from single mast cells. CFMA enabled the detection and quantification of discrete exocytotic events from single mast cells. Mast cells from two transgenic mouse models expressing human sickle hemoglobin (hBERK1 and BERK) and a control mouse expressing normal human hemoglobin (HbA-BERK) were monitored using CFMA to explore the impact of sickle-cell-induced inflammation and chronic morphine exposure on mast cell function. This work, utilizing the unique mechanistic perspective provided by CFMA, describes how mast cell function is significantly altered in hBERK1 and BERK mice, including decreased serotonin released compared to HbA-BERK controls. Furthermore, morphine was shown to significantly increase the serotonin released from HbA-BERK mast cells and demonstrated the capacity to reverse the observed sickle-cell-induced changes in mast cell function.
Source: ACS Chemical Biology
DOI: 10.1021/cb200347q
Institution: University of Minnesota
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1421860442, G1822506642, Opioid Activity in Endothelium in Sickle Cell Disease, G3009547223, Characteristics and mechanisms of pain in sickle cell disease, Vascular Pathobiology of Sickle Cell Disease, G696249762, Chemistry-Biology Interface Training Grant, IMMUNE SYSTEM-ON-A-CHIP FOR QUANTITATIVE ANALYSIS OF CELL INTERACTIONS DURING ALL
OpenAlex ID: W1990537250