Christopher Kepley

There are 50 included publications by Christopher Kepley :

TitleDateViewsBrief Description
“Accentuate the negative, eliminate the positive”: Engineering allergy therapeutics to block allergic reactivity through negative signaling 2008 8 By targeting the dominant-negative signaling receptor Fc?RIIb expressed on proallergic cells, we have developed 2 novel platforms for the treatment of IgE-mediated allergic disease. First is a genetically engineered bifunctional human fusion protein ...
Antigen-induced reduction in mast cell and basophil functional responses due to reduced Syk protein levels 2005 6 Background: The high-affinity IgE receptor, FceRI, is unresponsive on mast cells and basophils from people in several populations through an unknown mechanism. Similarly, FceRI-positive basophils from ‘nonreleasers’ are IgE-unresponsive and are defic...
Antigenic determinants of the bilobal cockroach allergen Bla g 2 2015 1 Bla g 2 is a major indoor cockroach allergen associated with the development of asthma. Antigenic determinants on Bla g 2 were analyzed by mutagenesis based on the structure of the allergen alone and in complex with monoclonal antibodies that interfe...
Application of Fullerenes in Nanomedicine: an Update 2013 2486 Fullerenes are carbon spheres presently being pursued globally for a wide range of applications in nanomedicine. These molecules have unique electronic properties that make them attractive candidates for diagnostic, therapeutic and theranostic applic...
C5a Receptor Enables Participation of Mast Cells in Immune Complex Arthritis Independently of Fc? Receptor Modulation 2010 787 Objective: Mast cells are tissue-resident immune sentinels that are implicated in the pathogenesis of inflammatory joint disease. The aim of this study was to test our hypothesis that complement fragments could be key activators of synovial mast cell...
A chimeric human-cat fusion protein blocks cat-induced allergy 2005 3 Animal allergens are an important cause of asthma and allergic rhinitis. We designed and tested a chimeric human-cat fusion protein composed of a truncated human IgG Fcg1 and the major cat allergen Fel d1, as a proof of concept for a new approach to ...
Chimeric human fcgamma-allergen fusion proteins in the prevention of allergy 2007 2 Allergic responses are strongly associated with Th2-type immune responses, and modulation of the skewed Th2 response toward a more balanced response is the major goal of allergen immunotherapy (IT) in allergic disorders. To achieve this goal, several...
Crystal structure of a dimerized cockroach allergen Bla g 2 complexed with a monoclonal antibody 2008 8 The crystal structure of a 1:1 complex between the German cockroach allergen Bla g 2 and the Fab' fragment of a monoclonal antibody 7C11 was solved at 2.8-Å resolution. Bla g 2 binds to the antibody through four loops that include residues 60-70, 83-...
Detection of MCT and MCTC Types of Human Mast Cells by Immunohistochemistry Using New Monoclonal Anti-tryptase and Anti-chymase Antibodies 1989 9 We developed an improved immunohistochemical technique for distinguishing human mast cells of the MCT (tryptase-positive, chymase-negative) and MCTC (tryptase-positive, chymase-positive) types utilizing a biotinylated murine anti-chymase monoclonal a...
Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways 2012 1062 Mast cells (MC) and peripheral blood basophils (PBB) are well known for their role in the allergic response mediated through high affinity IgE receptors (FceRI). However, these cells can also be stimulated by other non-allergic secretagogues to relea...
Environmental polycyclic aromatic hydrocarbons, benzo(a) pyrene (BaP) and BaP-quinones, enhance IgE-mediated histamine release and IL-4 production in human basophils 2003 3 Polycyclic aromatic hydrocarbons (PAHs) are major components of diesel exhaust particles found in pollutant respirable particles. There is growing evidence that these fossil fuel combustion products exacerbate allergic inflammation. Basophils contrib...
Epoxyeicosatrienoic acids are involved in the C70 fullerene derivative–induced control of allergic asthma 2012 1122 Background: Fullerenes are molecules being investigated for a wide range of therapeutic applications. We have shown previously that certain fullerene derivatives (FDs) inhibit mast cell (MC) function in vitro, and here we examine their in vivo therap...
Evidence for human mast cell nonreleaser phenotype 2003 2 Mast cells and basophils express high amounts of Fc?RI. In basophils the concentration of anti-IgE or antigen required for maximal histamine release through Fc?RI varies among donors, a concept termed “releasability.” Some donors fail to release hist...
FceRI–FcgRII Coaggregation inhibits IL-16 production from human langerhans-like dendritic cells 2003 2 Langerhans-like dendritic cells (LLDC) express the high-affinity IgE receptor FceRI form that lacks the ß-chain, and may play an important role in allergic inflammation via production of IL-16. Secretion of mediators by human mast cells and basophils...
Fullerene Antioxidants Decrease Organophosphate-induced Acetylcholinesterase Inhibition in vitro 2011 1319 Although organophosphate (OP)-induced acetylcholinesterase (AChE) inhibition is the critical mechanism causing toxicities that follow exposure, other biochemical events, including oxidative stress, have been reported to contribute to OP toxicity. Ful...
Fullerene Nanomaterials Inhibit Phorbol Myristate Acetate-induced Inflammation 2009 910 Inflammation is a natural biological response that occurs when vascular tissues are subjected to harmful stimuli. This process may be beneficial to the host during wound healing and infections but can be detrimental if left unchecked. Oxidative stres...
Fullerene nanomaterials potentiate hair growth 2009 1 Hair loss is a common symptom resulting from a wide range of disease processes and can lead to stress in affected individuals. The purpose of this study was to examine the effect of fullerene nanomaterials on hair growth. We used shaved mice as well ...
Fullerenes in Medicine; Will it ever Occur? 2012 21 Fullerenes represent a group of compounds having unique properties that make them attractivecandidates for use as a platform for developing new medical applications. The carbon cage(usually C60 and C70) of empty cage fullerenes (Figure 1-left/middle)...
Functionalization of Gadolinium Metallofullerenes for Detecting Atherosclerotic Plaque Lesions by Cardiovascular Magnetic Resonance 2013 970 Background: The hallmark of atherosclerosis is the accumulation of plaque in vessel walls. This process is initiated when monocytic cells differentiate into macrophage foam cells under conditions with high levels of atherogenic lipoproteins. Vulnerab...
Human Mast Cells from Adipose Tissue Target and Induce Apoptosis of Breast Cancer Cells 2019 2 2018-2019 UNCG University Libraries Open Access Publishing Fund Grant Winner.

Mast cells (MC) are important immune sentinels found in most tissue and widely recognized for their role as mediators of Type I hypersensitivity. However, they als...
Hydrochalarones: a novel endohedral metallofullerene platform for enhancing magnetic resonance imaging contrast 2008 2 Targeted imaging requires contrast agents that remain in the vasculature for extended periods of time. A new contrast agent is described in which gadolinium is encapsulated within an extremely stable carbon sphere, thus allowing for safe extended res...
Identification of the FceRI-activated tyrosine kinases Lyn, Syk, and Zap-70 in human basophils 1998 4 Background: In human blood basophils, cross-linking the high-affinity IgEreceptor FceRI with multivalent antigen activates a signaling pathway leading to Ca2+ mobilization, actin polymerization, shape changes, secretion, and cytokine production. Meth...
IL-33/ST2 axis promotes mast cell survival via BCLXL 2014 1187 Mast cells (MC) are potent innate immune cells that accumulate in chronically inflamed tissues. MC express the IL-33 receptor IL-1 receptor-related protein ST2 at high level, and this IL-1 family cytokine both activates MC directly and primes them to...
IL-4 selectively enhances FcgRIII expression and signaling on mouse mast cells 2003 0 Fc receptors for IgG (Fc?R) are widely expressed in the hematopoietic system and mediate a variety of inflammatory responses. There are two functional classes of FcgR, activation and inhibitory receptors. Since IgG immune complexes (IgG IC) bind each...
Immunohistochemical detection of human basophils in late-phase skin reactions 1998 3 Background: Human basophils are difficult to detect with classic histochemical stains at sites of allergic inflammation. The 2D7+ anti-basophil monoclonal antibody was used to identify basophils in skin during the late-phase response to a cutaneous a...
Immunologically mediated signaling in basophils and mast cells: finding therapeutic targets for allergic diseases in the human FceR1 signaling pathway 2000 2 The high affinity IgE receptor, FceRI, plays key roles in an array of acute and chronic human allergic reactions including asthma, allergic rhinitis, atopic dermatitis, urticaria and anaphylaxis. In humans and rodents, this receptor is found at high ...
In Vitro Desensitization of Human Skin Mast Cells 2012 961 Desensitization is a clinical procedure whereby incremental doses of a drug are administered over several hours to a sensitive patient until a therapeutic dose and clinical tolerance are achieved. Clinical tolerance may occur in part by attenuating t...
Inhibition of allergen-specific IgE reactivity by a human Ig Fcgamma-Fcepsilon bifunctional fusion protein 2004 1 Background: Coaggregating FceRI with FcgRII receptors holds great potential for treatment of IgE-mediated disease by inhibiting FceRI signaling. We have previously shown that an Fcg-Fce fusion protein, human IgG-IgE Fc fusion protein (GE2), could inh...
Inhibition of inflammatory arthritis using fullerene nanomaterials 2015 3 Inflammatory arthritis (e.g. rheumatoid arthritis; RA) is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their abi...
Liposomal formulation of amphiphilic fullerene antioxidants 2010 2 Novel amphiphilic fullerene[70] derivatives that are rationally designed to intercalate in lipid bilayers are reported, as well as its vesicular formulation with surprisingly high loading capacity up to 65% by weight. The amphiphilic C70 bisadduct fo...
Mast cell number and phenotype in chronic idiopathic urticaria 1995 2 Background: Increased levels of histamine have been previously demonstrated in patients with chronic idiopathic urticaria. Objective: The purpose of the study was to determine whether increased numbers of mast cells are present in lesional skin from ...
Modifications to an Fcgamma-Fcvarepsilon fusion protein alter its effectiveness in the inhibition of FcvarepsilonRI-mediated functions 2007 2 Background: GE2, a human bifunctional Fcg-Fce fusion protein cross-links FcgRIIb and FceRI on human mast cells and basophils and results in inhibition of FceRI-mediated functions. Objective: Three modified Fcg-Fce (GE) proteins were compared with GE2...
Negative regulation of FceRI signaling by FcgRII costimulation in human blood basophils 2000 5 Background: Signaling through the antigen receptors of human B and T cells and the high-affinity IgE receptor Fc-epsilonRI of rodent mast cells is decreased by cross-linking these receptors to the low-affinity IgG receptor Fc-gammaRIIB. The inhibiti...
New Approaches to Allergen Immunotherapy 2006 11 Allergic diseases are common problems affecting 20% to 30% of the US population. Mast cells and basophils are the primary effector cells mediating allergic inflammation through the triggering of membrane immunoglobulin E receptors (FceRI) with antige...
A New Class of Human Mast Cell and Peripheral Blood Basophil Stabilizers that Differentially Control Allergic Mediator Release 2010 1114 Treatments for allergic disease block the effects of mediators released from activated mast cells and blood basophils. A panel of fullerene derivatives was synthesized and tested for their ability to preempt the release of allergic mediators in vitro...
A new steroid-mimicking nanomaterial that mediates inhibition of human lung mast cells responses 2014 1 Water-soluble fullerenes can be engineered to regulate activation of mast cells (MC) and control MC-driven diseases in vivo. To further understand their anti-inflammatory mechanisms a C70-based fullerene conjugated to four myo-inositol molecules (C70...
NF-kappaB Inhibitors that Prevent Foam Cell Formation and Atherosclerotic Plaque Accumulation 2017 2 The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. ...
A novel human immunoglobulin Fcg–Fce bifunctional fusion protein inhibits FceRI-mediated degranulation 2002 2 Human mast cells and basophils that express the high-affinity immunoglobulin E (IgE) receptor, Fce receptor 1 (FceRI), have key roles in allergic diseases. FceRI cross-linking stimulates the release of allergic mediators1. Mast cells and basophils co...
Polyhydroxylated C60 fullerene (fullerenol) attenuates neutrophilic lung inflammation in mice 2008 2 Inflammation is crucial to eliminate pathogens and promote repair of injured tissue. However, excessive or persistent inflammation can contribute to tissue injury and the pathogenesis and exacerbation of diseases, including inflammatory lung diseases...
A Potential New Target for Asthma Therapy: A Disintegrin and Metalloprotease 10 (ADAM10) Involvement in Murine Experimental Asthma 2011 638 Background: Elevated levels of CD23, a natural regulator of IgE production, have been shown to decrease the signs of lung inflammation in mice. The aim of this study was to study the involvement of ADAM10, the primary CD23 sheddase, in experimental ...
Purification of human basophils by density and size alone 1994 7 Basophils typically account for approximately 1% of the white cells in peripheral blood. We have developed a unique method for purifying basophils from whole blood of normal subjects to at least 95% purity. Basophils are separated from other cell typ...
Regulation of human basophil adhesion to endothelium under flow conditions: Different very late antigen 4 regulation on umbilical cord blood-derived and peripheral blood basophils 2002 4 Background: Although soluble mediators released by basophils in tissue sites contribute to the chronic injury that occurs in hypersensitivity diseases, only limited information is available about how circulating basophils are recruited to tissues. In...
The Role of Horseshoe Crabs in the Biomedical Industry and Recent Trends Impacting Species Sustainability 2018 2 Every year the Atlantic horseshoe crab (Limulus polyphemus) arrives on shore to spawn, a sight once taken for granted. However, in addition to the gradual climate changes impacting all ecosystems, commercial demand from the widespread application of ...
Study Examining Fullerene Toxicity Raises Questions as to the Purity of the Nanomaterials and Erroneous Experimental Conclusions 2014 1 To the Editor, We are compelled to comment on a recent article in your journal “C60 Exposure Augments Cardiac Ischemia/Reperfusion Injury and Coronary Artery Contraction in Sprague Dawley Rats; 138(2), 365–378” by Thompson1 in which various conclusio...
Surface plasmon resonance: a label-free tool for cellular analysis 2015 1 Surface plasmon resonance (SPR) is a popular technique that allows for sensitive, specific, label-free and real-time assessment of biomolecular interactions. SPR is a nondestructive, modular and flexible tool for various applications in biomedical sc...
Syk deficiency in human non-releaser lung mast cells 2007 3 Human lung mast cells, like peripheral blood basophils, can have a non-releaser phenotype characterized by a failure to respond to FceRI-IgE-mediated stimulation [1]. Previous studies on human basophils demonstrated that approximately 10–15% of donor...
Syk deficiency in non-releaser basophils 1999 4 Background: Peripheral blood basophils from 10% to 20% of donors fail to degranulate in response to cross-linking the high-affinity IgE receptor FceRI. The molecular mechanisms underlying the nonreleaser phenotype have not been established. Objective...
A synthetic crustacean bait to stem forage fish depletion 2016 2 Crustaceans, such as crab and lobster, comprise an important global food commodity. They are captured in traps using primarily forage fish (e.g. anchovies, herring, and menhaden), as bait. Approximately 18 million tons of these fish are used annually...
TGFbeta1 induces mast cell apoptosis 2006 2 Mast cells are potent effectors of the inflammatory response, playing an important role in atopy, bacterial immunity, and animal models of arthritis, multiple sclerosis, and heart disease. Hence controlling mast cell numbers and responsiveness is ess...
Uptake and distribution of fullerenes in human mast cells 2010 2 Fullerenes are carbon cages of variable size that can be derivatized with various side chain moieties resulting in compounds that are being developed into nanomedicines. Although fullerene use in several preclinical in vitro and in vivo models of dis...