Biochemistry, Biophysics, and Structural Biology Commons^™

Intimate Attachment Of Escherichia Coli O157:H7 To Urinary Bladder Epithelium In The Gnotobiotic Piglet Model, Rodney A. Moxley, Tom W. Bargar, Stephen D. Kachman, Diane R. Baker, David H. Francis

School of Veterinary and Biomedical Sciences: Faculty Publications

Enterohemorrhagic Escherichia coli (EHEC), a pathogenic subset of Shiga toxin-producing E. coli (STEC), is an important cause of hemorrhagic colitis and hemolytic–uremic syndrome (HUS), and a rare cause of urinary tract infections (UTIs) with associated HUS. EHEC strains attach intimately to intestinal epithelium with formation of actin pedestals (attaching-effacing (A/E) lesions); however, the mechanism of EHEC attachment to the uroepithelium is unknown. We conducted a retrospective study on archived urinary bladder specimens from gnotobiotic piglets that naturally developed cystitis associated with EHEC O157:H7 infection following oral inoculation and fecal shedding. Paraffin-embedded bladder tissues from three piglets with cystitis and immunohistochemical …

Triggers Of Inflammatory Heart Disease, Ninaad Lasrado, Bharathi Yalaka, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Inflammatory heart disease (IHD) is a group of diseases that includes pericarditis, myocarditis, and endocarditis. Although males appear to be more commonly affected than females, IHD can be seen in any age group. While the disease can be self-limiting leading to full recovery, affected individuals can develop chronic disease, suggesting that identification of primary triggers is critical for successful therapies. Adding to this complexity, however, is the fact that IHD can be triggered by a variety of infectious and non-infectious causes that can also occur as secondary events to primary insults. In this review, we discuss the immunological insights into …

Current Status Of Zika Virus Vaccines: Successes And Challenges, Aryamav Pattnaik, Bikash R. Sahoo, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global research community to understand the immunopathogenic mechanisms of the virus and rapidly develop safe and efficacious vaccines. This has led to a number of ZIKV vaccine candidates that have shown significant promise in human clinical trials. These candidates include nucleic acid vaccines, inactivated vaccines, viral-vectored vaccines, and attenuated vaccines. Additionally, a number of vaccine candidates have been …

Rapid Differentiation Of Moraxella Bovoculi Genotypes 1 And 2 Using Maldi-Tof Mass Spectrometry Profiles, Matthew M. Hille, Aaron M. Dickey, Kara Robbins, Michael L. Clawson, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovoculi is the most frequently isolated bacteria from the eyes of cattle with Infectious Bovine Keratoconjunctivitis (IBK), also known as bovine pinkeye. Two distinct genotypes of M. bovoculi, genotype 1 and genotype 2, were characterized after whole genome sequencing showed a large degree of single nucleotide polymorphism (SNP) diversity within the species. To date, both genotypes have been isolated from the eyes of cattle without clinical signs of IBK while only genotype 1 strains have been isolated from the eyes of cattle with clinical signs of IBK. We used 38 known genotype 1 strains and 26 known genotype …

Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog

Wayne State University Dissertations

The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …

Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan

Articles

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).

Evaluating A Culprit: A Review Of The Biochemical Mechanisms Of Non-Celiac Gluten Intolerance, Callie Cinque

Honors Theses

Non-Celiac Gluten Intolerance (NCGI) has evaded biological and chemical mechanisms since it was first reported in 1978. Celiac Disease, a multi-system immune mediated disorder has long served as the most similar counterpart to NCGI. Less cases of celiac disease are going undiagnosed reflecting an improvement on sensitive and decisive diagnostic tools. However, NCGI has been significantly growing as a diagnosis over the past decade with little match or similarity to the markers found in celiac disease patients. Critical evaluation of NCGI theories, experimentation, and existing hypotheses is necessary. This review seeks to synthesize multiple disciplines of gluten research and enhance …

Therapeutic Dna: Delivery And As A Delivery Vehicle, Natalie J. Holl

Masters Theses

"A review of gene delivery methods and gene editing methods, as well as original research utilizing DNA as a delivery vehicle is presented in the following thesis. Thousands of diseases have been linked to genes. Gene therapy, either delivering therapeutic genes or editing DNA bases, has arisen as a treatment option with the potential to cure diseases, rather than just ease symptoms. Genes and editing tools need to be delivered to cells for these therapies to be effective and many techniques have been developed to address the issue of delivery. Nonviral and viral methods have been used to deliver nucleic …

Genomic-Based Identification Of Environmental And Clinical Listeria Monocytogenes Strains Associated With An Abortion Outbreak In Beef Heifers, Katherine J. Whitman, James L. Bono, Michael L. Clawson, John D. Loy, Joseph M. Bosilevac, Terrance M. Arthur, Jeff D. Ondrak

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: In a beef cattle facility an outbreak of abortions occurred over a 36-day period and included samples from two aborted (non-viable) fetuses and 21 post-abortion clinical cases. There are numerous etiologies, including clinical listeriosis. At the species level, Listeria monocytogenes is ubiquitous in cattle production environments, including soil, feed, and occasionally water sources, and is a common enteric resident of cattle and other mammals. There are four genetically distinct lineages of L. monocytogenes (I-IV), with most lineage III and IV isolates obtained from ruminants. Definitive diagnosis of L. monocytogenes as a causative agent in disease outbreaks relies upon case …

Molecular And Functional Characterization Of Α-Galactosyl Epitopes In Trypanosoma Cruzi, Uriel Ortega Rodriguez

Open Access Theses & Dissertations

Trypanosoma cruzi, the causative agent of Chagas disease (CD) currently affects 6-7 million people across the world. Currently, only two drugs, benznidazole and nifurtimox, are available for treatment of CD and they are highly toxic and less effective in the chronic stage of the disease. Specific biomarkers for diagnosis and follow-up of treatment do not exist in the clinical settings. following chemotherapy, patients take approximately 10-20 years to exhibit negative seroconversion with the conventional serology assays. Moreover, there is no vaccine available to prevent or treat CD. T. cruzi contains a complex cell surface consisting of several classes of glycoconjugates …

Pneumovirus Infections: Understanding Rsv And Hmpv Entry, Replication, And Spread, Jonathan T. Kinder

Theses and Dissertations--Molecular and Cellular Biochemistry

Pneumoviruses including human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are significant causes of respiratory tract infections globally. Children, elderly, and immunocompromised patients are at the greatest risk for developing severe infections, which can have devastating outcomes. Although these viruses are ubiquitous with significant impacts on human health, there are no antivirals or vaccines available. The only FDA approved therapy is a monoclonal antibody for RSV, given prophylactically during the infectious season, and this treatment is only available for high risk infants. The work presented in this thesis aims to increase our understanding of how these viruses enter, replicate, and …

Eecp Improves Markers Of Functional Capacity Regardless Of Underlying Ranolazine Therapy, Sanaz Ziad, Jamil Malik, Obinna Isiguzo, Lang Xu, Leqi Chen, Annette Cox, Sachin Shah

School of Pharmacy Faculty Articles

OBJECTIVE: Enhanced external counterpulsation (EECP) and ranolazine are approved treatments for patients with chronic stable angina by the United States Food and Drug Administration (FDA). Whether EECP offers clinical benefits regardless of underlying ranolazine therapy needs further investigation.

METHODS: This was a retrospective evaluation of patients referred to a specialized EECP center. Patients having data on 6-Minute Walk Distance (6MWD) or Duke Activity Status Index (DASI) were categorized into two groups (EECP with ranolazine or EECP only). The primary endpoints were change in 6MWD and DASI before and after a full course of EECP within each of the two groups. …

Modulation Of K V 7 Channel Deactivation By Pi(4,5)P 2, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The activity of K_V7 channels critically contributes to the regulation of cellular electrical excitability in many cell types. In the central nervous system, the heteromeric K_V7.2/K_V7.3 channel is thought to be the chief molecular entity giving rise to M-currents. These K⁺-currents as so called because they are inhibited by the activation of Gq protein-coupled muscarinic receptors. In general, activation of Gq protein-coupled receptors (GqPCRs) decreases the concentration of the phosphoinositide PI(4,5)P₂ which is required for K_V7 channel activity. It has been recently reported that the deactivation rate of K …

Uterine Torsion Dystocia Complicated By Perosomus Elumbis In An Angus Calf Associated With A Consanguineous Mating, Alyssa B. Helms, Riley E. Thompson, Sam Lawton, Jessica L. Petersen, Allison Watson, Mee-Ja Sula, David J. Steffen, Brian K. Whitlock

School of Veterinary and Biomedical Sciences: Faculty Publications

A six-year-old multiparous Angus cow was presented for dystocia. Vaginal and rectal examinations revealed an approximately 360° counterclockwise uterine torsion. The torsion was corrected by rolling the cow counterclockwise (three episodes) with the aid of a plank coupled with manual detorsion via the vagina. The placement of obstetric chains followed by manual traction ultimately delivered a stillborn male calf with evidence of vertebral aplasia, arthrogryposis, and abdominal organ herniation. Patient history and subsequent parentage verification revealed that the calf was the result of a consanguineous (mother to son) mating. Tissue samples from the affected calf and blood samples from the …

Identification Of Immunogenic Epitopes That Permit The Detection Of Antigen-Specific T Cell Responses In Multiple Serotypes Of Group B Coxsackievirus Infections, Ninaad Lasrado, Arunakumar Gangaplara, Rajkumar Arumugam, Chandirasegara Massilamany, Sayli Pokal, Yuzhen Zhou, Shi-Hua Xiang, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Coxsackievirus group B (CVB) contains six serotypes that can affect various organs. Some of these organ-specific diseases such as myocarditis and pancreatitis can be caused by more than one serotype. Thus, development of immunological tools common to multiple serotypes is desired. This is especially critical for analyzing antigen-specific T cell responses at a single cell level. To this end, we made efforts to identify the immunogenic epitopes of CVB3 leading us to localize three T cell epitopes within the viral protein 1 (VP1) namely, VP1 681–700, VP1 721–740 and VP1 771–790. First, we confirmed their immunogenicity in the immunization settings. …

First Records Of Established Populations Of Ixodes Scapularis (Acari: Ixodidae) Collected From Three Nebraska Counties, Lindsey E. Nielsen, Roberto Cortinas, Paul D. Fey, Peter C. Iwen, David H. Nielsen

School of Veterinary and Biomedical Sciences: Faculty Publications

Reported cases of Lyme disease in Nebraska have been assumed to be imported from other endemic areas. Previous surveillance efforts provided no evidence of established populations as only individual specimens of Ixodes scapularis (Say) had been collected. In the winter of 2018, adult I. scapularis were found on a dog at Two Rivers State Recreation Area, Douglas County, prompting tick collection at the site and nearby natural areas. In May 2019, all life stages of host-seeking I. scapularis were collected using dragging and flagging techniques in sites located near the Platte River in Douglas, Sarpy, and Saunders counties. This is …

Methods Of Treating Or Preventing Zika Virus Infection, Shi-Hua Xiang, Nicholas Palermo, Asit K. Pattnaik, Aryamay Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

This document relates to methods and materials for treating a mammal having a Zika virus (ZIKV) infection. For example, a composition including one or more non-nucleoside RNA polymerase inhibitors can be administered to a mammal having, or at risk of developing, a ZIKV infection to treat the mammal.

Recent Advances In The Diagnosis Of Classical Swine Fever And Future Perspectives, Lihua Wang, Rachel Madera, Yuzhen Li, D. Scott Mcvey, Jishu Shi

School of Veterinary and Biomedical Sciences: Faculty Publications

Classical swine fever (CSF) is a highly contagious viral disease of pigs, including wild boar. It is regarded as one of the major problems in the pig industry as it is still endemic in many regions of the world and has the potential to cause devastating epidemics, particularly in countries free of the disease. Rapid and reliable diagnosis is of utmost importance in the control of CSF. Since clinical presentations of CSF are highly variable and may be confused with other viral diseases in pigs, laboratory diagnosis is indispensable for an unambiguous diagnosis. On an international level, well-established diagnostic tests …

Evaluation Of A Baculovirus-Expressed Vp2 Subunit Vaccine For The Protection Of White-Tailed Deer (Odocoileus Virginianus) From Epizootic Hemorrhagic Disease, Sun Young Sunwoo, Leela E. Noronha, Igor Morozov, Jessie D. Trujilo, In Joong Kim, Erin E. Schirtzinger, Bonto Faburary, Barbara S. Drolet, Kinga Urbaniak, D. Scott Mcvey, David A. Meekins, Mitchell V. Palmer, Velmurugan Balaraman, William C. Wilson, Juergen A. Richt

School of Veterinary and Biomedical Sciences: Faculty Publications

Epizootic hemorrhagic disease virus (EHDV) is an arthropod-transmitted RNA virus and the causative agent of epizootic hemorrhagic disease (EHD) in wild and domestic ruminants. In North America, white-tailed deer (WTD) experience the highest EHD-related morbidity and mortality, although clinical disease is reported in cattle during severe epizootics. No commercially licensed EHDV vaccine is available in North America. The objective of this study was to develop and evaluate a subunit vaccine candidate to control EHD in WTD. Recombinant VP2 (rVP2) outer capsid proteins of EHDV serotypes 2 (EHDV-2) and 6 (EHDV-6) were produced in a baculovirus-expression system. Mice and cattle vaccinated …

Amphiphilic Cyclobutenes And Cylobutanes, Wantanee Sittiwong, Patrick H. Dussault, Raul G. Barletta, Robert Powers

School of Veterinary and Biomedical Sciences: Faculty Publications

This disclosure relates to amphiphilic compounds containing a cyclobutene or cyclobutane moiety. In some embodiments, the compounds are useful for treating infection by Mycobacterium such as Mycobacterium tuberculosis. Cyclobutene containing compounds are also useful as monomers in the preparation of amphiphilic polymers.

Non-Neuroinvasivevirusesand Uses Thereof, Gregory A. Smith, Patricia J. Sollars, Gary E. Pickard, Ekaterina E. Heldwein

School of Veterinary and Biomedical Sciences: Faculty Publications

Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.

Mitochondrial Metabolism In Astrocytes Regulates Brain Bioenergetics, Neurotransmission And Redox Balance, Jordan Rose, Christian Brian, Aglaia Pappa, Mihalis I. Panayiotidi, Rodrigo Franco

School of Veterinary and Biomedical Sciences: Faculty Publications

In the brain, mitochondrial metabolism has been largely associated with energy production, and its dysfunction is linked to neuronal cell loss. However, the functional role of mitochondria in glial cells has been poorly studied. Recent reports have demonstrated unequivocally that astrocytes do not require mitochondria to meet their bioenergetics demands. Then, the question remaining is, what is the functional role of mitochondria in astrocytes? In this work, we review current evidence demonstrating that mitochondrial central carbon metabolism in astrocytes regulates overall brain bioenergetics, neurotransmitter homeostasis and redox balance. Emphasis is placed in detailing carbon source utilization (glucose and fatty acids), …

Mechanisms Of Sex Hormones In Autoimmunity: Focus On Eae, Ninaad Lasrado, Ting Jia, Chandirasegaran Massilamany, Rodrigo Franco, Zsolt Illes, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Sex-related differences in the occurrence of autoimmune diseases is well documented, with females showing a greater propensity to develop these diseases than their male counterparts. Sex hormones, namely dihydrotestosterone and estrogens, have been shown to ameliorate the severity of inflammatory diseases. Immunologically, the beneficial effects of sex hormones have been ascribed to the suppression of effector lymphocyte responses accompanied by immune deviation from pro-inflammatory to anti-inflammatory cytokine production. In this review, we present our view of the mechanisms of sex hormones that contribute to their ability to suppress autoimmune responses with an emphasis on the pathogenesis of experimental autoimmune encephalomyelitis.

Evidence For Anti-Viral Effects Of Complete Freund’S Adjuvant In The Mouse Model Of Enterovirus Infection, Arunakumar Gangaplara, Chandirasegaran Massilamany, Ninaad Lasrado, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Group B coxsackieviruses (CVBs) belonging to the genus, Enterovirus and contain six serotypes that induce various diseases, whose occurrence may involve the mediation of more than one serotype. We recently identified immunogenic epitopes within coxsackieviruses B3 (CVB3) viral protein 1 that induce anti-viral T cell responses in mouse models of CVB infections. In our investigations to determine the protective responses of the viral epitopes, we unexpectedly noted that animals immunized with complete Freund’s adjuvant (CFA) alone and later challenged with CVB3 were completely protected against myocarditis. Similarly, the pancreatitis-inducing ability of CVB3 was remarkably reduced to only 10% in the …

Porcine Reproductive And Respiratory Syndrome Virus Reverse Genetics And The Major Applications, Jayeshbhai Chaudhari, Hiep Vu

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the late 1980s and became endemic in most swine producing countries, causing substantial economic losses to the swine industry. The first reverse genetics system for PRRSV was reported in 1998. Since then, several infectious cDNA clones for PRRSV have been constructed. The availability of these infectious cDNA clones has facilitated the genetic modifications of the viral genome at precise locations. Common approaches to manipulate the viral genome include site-directed mutagenesis, deletion of viral genes or …

An Evidence For Surface Expression Of An Immunogenic Epitope Of Sarcoplasmic/Endoplasmic Reticulum Calcium-Atpase2a On Antigen-Presenting Cells From Naive Mice In The Mediation Of Autoimmune Myocarditis, Rajkumar Arumugam, Bharathi Yalaka, Chandirasegara Massilamany, Ms Shihabudeen Haider Ali, Ninaad Lasrado, Sabarirajan Jayaraja, Jean-Jack Riethoven, Xinghui Sun, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

We recently reported identification of sarcoplasmic/endoplasmic reticulum calcium-ATPase2a (SERCA2a) 971–990, which induces atrial myocarditis by generating autoreactive T cells in A/J mice. However, it was unknown how antigen-sensitized T cells could recognize SERCA2a 971–990, since SERCA2a-expression is confined to an intracellular compartment. In this report, we present evidence that antigen-presenting cells (APCs) from lymphoid and non-lymphoid organs in naïve animals present SERCA2a 971–990 and stimulate antigen-specific T cells. Using major histocompatibility complex (MHC) class II dextramers for SERCA2a 971–990, we created a panel of T cell hybridomas and demonstrated that splenocytes from naïve A/J mice stimulated the hybridoma cells without …

Viral Myocarditis Involves The Generation Of Autoreactive T Cells With Multiple Antigen Specificities That Localize In Lymphoid And Non-Lymphoid Organs In The Mouse Model Of Cvb3 Infection, Rakesh H. Basavalingappa, Rajkumar Arumugam, Ninaad Lasrado, Bharathi Yalaka, Chandirasegara Massilamany, Arunakumar Gangaplara, Jean-Jack Riethoven, Shi-Hua Xiang, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Autoreactive T cells may contribute to post-viral myocarditis induced with Coxsackievirus B3 (CVB3), but the underlying mechanisms of their generation are unclear. Here, we have comprehensively analyzed the generation of antigen-specific, autoreactive T cells in the mouse model of CVB3 infection for antigens implicated in patients with myocarditis/dilated cardiomyopathy. First, comparative analysis of CVB3 proteome with five autoantigens led us to identify three mimicry epitopes, one each from adenine nucleotide translocator 1 (ANT), sarcoplasmic/ endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and cardiac troponin I. None of these induced cross-reactive T cell responses. Next, we generated major histocompatibility complex (MHC) class …

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …

Role Of Ciliary Proteins Adp Ribosylation Factor Like Gtpase 13b (Arl13b) And Bardet-Biedl Syndrome-8 (Bbs8) In Photoreceptor Outer Segment Morphogenesis, Maintenance, And Viability, Tanya L. Dilan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Photoreceptor neurons are modified primary cilia with an extended ciliary compartment known as the outer segment (OS). The mechanisms behind the elaboration of photoreceptor cilia, OS morphogenesis, and maintenance remain poorly understood. In this work, we focused on dissecting the role of two ciliary proteins, the small GTPase ADP-ribosylation factor-like GTPase 13B (ARL13B) and Bardet-Biedl Syndrome-8 (BBS8) in the context of photoreceptor biology. Both BBS8 and ARL13B are linked to defects in ciliogenesis (cilia development) and Retinitis Pigmentosa (vision loss). ARL13B is implicated in regulating ciliary length, and BBS8 is part of the Bardet-Biedl Syndrome complex (BBSome); the BBSome is …

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …