- Immune Response and Inflammation
- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Asthma and respiratory diseases
- Immune cells in cancer
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immunotherapy and Immune Responses
- Neonatal Respiratory Health Research
- T-cell and B-cell Immunology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cytokine Signaling Pathways and Interactions
- Inflammatory mediators and NSAID effects
- Wound Healing and Treatments
- Parasites and Host Interactions
- Sepsis Diagnosis and Treatment
- Venous Thromboembolism Diagnosis and Management
- S100 Proteins and Annexins
- Respiratory Support and Mechanisms
- interferon and immune responses
- IL-33, ST2, and ILC Pathways
- Blood Coagulation and Thrombosis Mechanisms
- Pulmonary Hypertension Research and Treatments
- Liver physiology and pathology
- Inflammation biomarkers and pathways
University of Michigan
2015-2024
Michigan United
2009-2023
Michigan Medicine
1995-2022
Christie's
2015
Queensland University of Technology
2012
Ann Arbor Center for Independent Living
1995-2011
Uppsala University
2009
Pulmonary and Critical Care Associates
2000-2008
Pulmonary Vascular Research Institute
2006
National Heart Lung and Blood Institute
2005
Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized persistent angiogenesis. The possibility was tested that interleukin-8 (IL-8), which is a cytokine chemotactic for lymphocytes and neutrophils, also angiogenic. Human recombinant IL-8 potently angiogenic when implanted rat cornea induced proliferation chemotaxis human umbilical vein endothelial cells. activity present conditioned media inflamed rheumatoid...
In this study, we demonstrate that the CXC family of chemokines displays disparate angiogenic activity depending upon presence or absence ELR motif. containing motif (ELR-CXC chemokines) were found to be potent factors, inducing both <i>in vitro</i> endothelial chemotaxis and vivo</i> corneal neovascularization. contrast, lacking motif, platelet factor 4, interferon γ-inducible protein 10, monokine induced by γ-interferon, not only failed induce significant cell neovacularization but...
Accumulation of polymorphonuclear neutrophils during the acute inflammatory response may exacerbate tissue injury through release activated oxygen products or proteolytic enzymes both. To assess role in myocardial infarction, circulating neutrophil levels dogs were reduced by 77 +/- 2% (mean SEM) administering rabbit antiserum to dog neutrophils. Acute infarction was induced open-chest anesthetized 90 minutes left circumflex coronary artery occlusion followed 6 hours reperfusion. Dogs...
Monocyte chemoattractant protein 1 (MCP-1) is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural killer cells. Because other chemokines have similar target cell specificities because CCR2, cloned MCP-1 receptor, binds ligands, it has been uncertain whether plays unique role in recruiting mononuclear cells vivo. To address this question, we disrupted SCYA2 (the gene encoding MCP-1) tested MCP-1–deficient mice models of inflammation. Despite normal numbers circulating...
Cytokines are recognized as critical early mediators of organ injury. We attempted to determine whether or not severe hepatic ischemia/reperfusion injury results in tumor necrosis factor-alpha (TNF-alpha) release with subsequent local and systemic tissue After 90 min lobar ischemia, TNF was measurable during the reperfusion period plasma all 14 experimental animals, levels peaking between 9 352 pg/ml. Endotoxin undetectable these animals. Pulmonary injury, evidenced by a neutrophilic...
Movement of neutrophils from the bloodstream to inflamed tissue depends on activation both neutrophil and endothelial cell. Endothelial cells lining postcapillary venule respond proinflammatory mediators by expressing adhesion molecules synthesizing a variety neutrophil-activating factors. cell production 77-amino acid variant interleukin-8 (IL-8) was found be requirement for invasion through vessel wall model. IL-8 secreted cytokine- or lipopolysaccharide-stimulated induced rapid shedding...
Human endothelial cells produced a neutrophil chemotactic factor (NCF) upon stimulation with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), or lipopolysaccharide (LPS). The expression of cell-derived NCF messenger RNA and biological activity was both time- concentration-dependent. Maximal mRNA occurred at 10 2 nanograms per milliliter for TNF IL-1β, respectively; first observed 1 hour after maintained least 24 hours. In situ hybridization analysis showed that peaked in treated by...
Cellular constituents of the alveolar-capillary wall may be key participants in recruitment polymorphonuclear leukocytes to lung through generation novel neutrophil chemotactic peptide interleukin-8 (IL-8). This interaction appears occur via ability human alveolar macrophage (AM)-derived monokines, tumor necrosis factor (TNF), and interleukin-1 (IL-1) induce gene expression IL-8 from pulmonary type II-like epithelial cells (A549). Northern blot analysis demonstrated that steady-state mRNA...
Tumor necrosis factor-alpha (TNF) is a macrophage-derived peptide that known to be an important mediator in various physiologic and immunologic events. Although the effector function of TNF has received recent attention, there relatively little information regarding factors regulate expression. Highly Ia-positive murine peritoneal macrophages obtained via complete Freund's adjuvant elicitation were challenged with lipopolysaccharide (LPS) assessed for production regulation at cellular...
Cells within the synovial tissue may recruit mononuclear phagocytes into fluid and tissues of arthritic patients. We investigated production chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1) using sera, fluid, tissue, as well macrophages fibroblasts isolated from 80 MCP-1 levels were significantly higher (P less than 0.05) in RA patients (mean 25.5 +/- 8.1 ng/ml [SE]) compared to osteoarthritis (OA) (0.92 0.08), or with other arthritides (2.9 1.5). sera (8.44 2.33) greater...
A number of novel chemotactic cytokines are becoming increasingly recognized as important participants in the elicitation specific inflammatory cells from peripheral blood to sites inflammation. Recent observations have now demonstrated that certain possess specificity for selected movement individual immune/inflammatory cell populations. One more studied is a neutrophil factor identified interleukin-8 (IL-8). This polypeptide mediator produced abundance by mononuclear phagocytic cells, well...
Ligands from dying cells are a source of Toll-like receptor (TLR) activating agents. Although TLR3 is known to respond RNA necrotic cells, the relative importance this response in vivo during acute inflammatory processes has not been fully explored. We observed involvement activation experimental polymicrobial septic peritonitis and ischemic gut injury absence an exogenous viral stimulus. In TLR3-deficient mice, increased chemokine/cytokine levels neutrophil recruitment characterized initial...
Accumulating evidence supports the hypothesis that neuroendocrine hormones may participate in immunologic processes. In our study we have determined UK-14304 (UK) and norepinephrine (NE), both alpha 2-adrenergic agonists, can augment LPS-stimulated TNF from elicited macrophages (MO). The increase production was concentration dependent with an EC50 for UK NE of 8.1 +/- 2.6 0.52 0.17 nM, respectively. concentration-effect curve shifted to right by 2-antagonist yohimbine (10(-6) M), new 49.7...
The present study was designed to elucidate the effects of chemokine monocyte chemoattractant protein (MCP-1) on blood–brain barrier (BBB) permeability. Experiments were conducted under in vitro conditions (coculture brain endothelial cells and astrocytes) cellular MCP-1 vivo (intracerebral intracerebroventricular administration MCP-1) potential contribution BBB disruption vivo. Our results showed that induces a significant increase permeability surface area product for fluorescein...
Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal disorder. Fibroplasia deposition of extracellular matrix are dependent, in part, on angiogenesis. We postulated that an imbalance exists the expression angiogenic (IL-8) vs angiostatic (IFN-gamma-inducible protein (IP-10)) CXC chemokines, which favors net angiogenesis IPF. To test this hypothesis, we obtained open lung biopsies either from normal patients undergoing thoracic surgery for reasons other than interstitial disease...
Many acute and chronic lung diseases are characterized by the presence of increased numbers activated macrophages. These macrophages derived predominantly from newly recruited peripheral blood monocytes may play a role in amplification perpetuation an initial insult. The process inflammatory cell recruitment is poorly understood, although expression cell-specific chemoattractants subsequent generation chemotactic gradients likely involved. Although immune cells such as lymphocytes known to...
A new neutrophil-activating peptide, termed ENA-78, was identified in the conditioned media of stimulated human type II epithelial cell line A549. In response to stimulation with either interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF-alpha), ENA-78 produced and secreted concomitantly IL-8, GRO alpha, gamma. consists 78 amino acids [sequence; see text] has a molecular weight 8,357. It four cysteines positioned identically those IL-8 analogues, thus belongs CXC family...