A5080219607- Chronic Obstructive Pulmonary Disease (COPD) Research
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neonatal Respiratory Health Research
- Respiratory Support and Mechanisms
- Asthma and respiratory diseases
- Inhalation and Respiratory Drug Delivery
- Blood disorders and treatments
- Pediatric health and respiratory diseases
- Immune cells in cancer
- Pneumonia and Respiratory Infections
- S100 Proteins and Annexins
- Blood transfusion and management
- Protease and Inhibitor Mechanisms
- Sepsis Diagnosis and Treatment
- Platelet Disorders and Treatments
- Phagocytosis and Immune Regulation
- Cellular Mechanics and Interactions
- Respiratory viral infections research
- Immune Cell Function and Interaction
- Cystic Fibrosis Research Advances
- Neuropeptides and Animal Physiology
- Antimicrobial Peptides and Activities
- Respiratory and Cough-Related Research
Lung Institute
2016-2025
University of North Carolina at Chapel Hill
2016-2025
Rainbow Babies & Children's Hospital
2001-2024
UNC Lineberger Comprehensive Cancer Center
2012-2024
Pulmonary and Critical Care Associates
2012-2022
University of North Carolina Health Care
2021
John Wiley & Sons (United States)
2018-2019
Indiana University School of Medicine
1994-2017
Cystic Fibrosis Foundation
2014
Segeberger Kliniken
2012
Neutrophil (PMN) migration in the systemic and pulmonary circulation of rabbits was compared by using different inflammatory stimuli to determine role leukocyte adhesion complex, CD11/CD18, each these vascular beds. The complex blocked administering anti-CD18 mAb 60.3. data show that 60.3 blocks PMN emigration into foci abdominal wall produced implanting sponges containing either hydrochloric acid, Streptococcus pneumoniae, Escherichia coli endotoxin, or PMA. also inhibited response...
During the initial phase of inflammatory response, leukocytes marginate and roll along endothelial surface, a process mediated largely by selectins their ligands. Mice with mutations in individual show no spontaneous disease have mild or negligible deficiencies responses. In contrast, we find that mice null both (P E) develop phenotype leukocyte adhesion deficiency characterized mucocutaneous infections, plasma cell proliferation, hypergammaglobulinemia, severe rolling cremaster venules...
Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on airway surfaces hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation with muco-obstructive lung diseases. Under this it postulated high produces sputum progression are characteristic bronchitis.We COPD status 917 participants from Subpopulations Intermediate Outcome Measures...
Staphylococcus aureus is a dangerous pathogen that can cause necrotizing infections characterized by massive inflammatory responses and tissue destruction. Staphylococcal α-hemolysin an essential virulence factor in severe S. pneumonia. It activates the nucleotide-binding domain leucine-rich repeat containing gene family, pyrin 3 (NLRP3) inflammasome to induce production of interleukin-1β programmed necrotic cell death. We sought determine role α-hemolysin-mediated activation NLRP3...
MUC5AC and MUC5B are the predominant gel-forming mucins in mucus layer of human airways. Each mucin has distinct functions site-specific expression. However, regional distribution expression cell types that secrete each normal/healthy airways not fully understood.
Mice with X-linked chronic granulomatous disease (CGD) generated by targeted disruption of the gp91phox subunit NADPH–oxidase complex (X-CGD mice) were examined for their response to respiratory challenge Aspergillus fumigatus. This opportunistic fungal pathogen causes infection in CGD patients due deficient generation neutrophil burst oxidants important damaging A. fumigatus hyphae. Alveolar macrophages from X-CGD mice found kill conidia vitro as effectively alveolar wild-type mice....
Neutrophils [polymorphonuclear leukocytes (PMNs)] are sequestrated in the lung capillary bed because PMNs delayed with respect to red blood cells (RBCs) as they pass through these microvessels. The present study examines circulating PMN size relation distribution of segment diameters human, dog, and rabbit lungs compares shape suspension that found within pulmonary capillaries. data show 61, 67, 38% segments narrower than mean diameter spherical rabbit, respectively. They also deform from a...
Neutrophil emigration during an inflammatory response is mediated through interactions between adhesion molecules on endothelial cells and neutrophils.P-Selectin mediates rolling or slowing of neutrophils, while intercellular adhe- sion molecule-i (ICAM-1) contributes to the firm neutrophils.Removing function either molecule partially prevents neutrophil emigration.To analyze further role P-selectin ICAM-1, we have generated a line mice with mutations in both these molecules.While mutation...
To determine the role of CD11/CD18 complexes in neutrophil emigration, inflammation was induced skin, lungs, or peritoneum mutant mice deficient CD18 (CD18−/− mutants). Peripheral blood CD18−/− mutants contained 11-fold more neutrophils than did wild-type (WT) mice. During irritant dermatitis by topical application croton oil, number emigrated histological sections dermis 98% less WT Streptococcus pneumoniae pneumonia, emigration not reduced. These data are consistent with expectations based...
ABSTRACT The lungs are an important site of host defense. capillary blood contains increased concentration neutrophils and other leukocytes compared with large vessels, due to the structure pulmonary bed, diameter spherical leukocytes, their poor deformability erythrocytes. During inflammation within distal airways, sequester capillaries emigrate into parenchyma. This sequential process involves complex events regulating interactions between mechanical adhesive properties both endothelial...
NF-kappaB binding sites are present in the promoter regions of many acute phase and inflammatory response genes, suggesting that plays an important role initiation innate immune responses. However, targeted mutations various family members have yet to identify responsible for this critical role. RelA-deficient mice die on embryonic day 15 from TNF-alpha-induced liver degeneration. To investigate importance RelA immunity, we genetically suppressed lethality by breeding deficiency onto a TNFR...
This study examined the effectiveness of antisense oligonucleotides targeted to intercellular adhesion molecule-1 (ICAM-1) inhibit endotoxin-induced upregulation ICAM-1 and neutrophil emigration compared apparent role when using oligonucleotides, anti-ICAM-1 antibodies, mutant mice. Antisense inhibited mRNA at 4 24 h after instillation endotoxin in a dose-dependent manner. Neutrophil into alveolar spaces was by 59%, similar inhibition antibodies 3E2 (58%) YN1/1 (75%). No observed wild-type...
The size and location of the marginated pool neutrophils (PMNs) in rabbit lungs were evaluated, rate exchange PMNs with circulating was determined. 99mTc-labeled erythrocytes (99mTc-RBCs) 125I-labeled macroaggregated albumin (125I-MAA) used to determine RBC transit times pulmonary circulation. Radiolabeled studied on their first passage through lungs. After 10 min circulation, fixed, gamma counted, prepared for morphometric autoradiographic studies; 74 +/- 3% retained passage, 23 2% within...
Novel proteomics platforms, such as the aptamer-based SOMAscan platform, can quantify large numbers of proteins efficiently and cost-effectively are rapidly growing in popularity. However, comparisons to conventional immunoassays remain underexplored, leaving investigators unsure when cross-assay appropriate. The correlation results from with relative protein quantification is explored by SOMAscan. For 63 assessed two chronic obstructive pulmonary disease (COPD) cohorts, subpopulations...
Rationale: Chronic obstructive pulmonary disease exacerbations are associated with progression, higher healthcare cost, and increased mortality. Published predictors of future include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, gastroesophageal reflux.Objectives: To determine the value adding blood biomarkers to clinical variables predict exacerbations.Methods: Subjects from SPIROMICS (Subpopulations Intermediate Outcomes Measures in COPD Study) (n =...
Rationale: The relative roles of mucus plugs and emphysema in mechanisms airflow limitation hypoxemia smokers with chronic obstructive pulmonary disease (COPD) are uncertain.Objectives: To relate image-based measures to obstruction oxygenation patients COPD.Methods: We analyzed computed tomographic (CT) lung images function participants the Subpopulations Intermediate Outcome Measures COPD Study. Radiologists scored on CT images, imaging software automatically quantified percentage....