A5091556449- Complement system in diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Blood Coagulation and Thrombosis Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Blood groups and transfusion
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Glycosylation and Glycoproteins Research
- Asthma and respiratory diseases
- Adenosine and Purinergic Signaling
- Drug Transport and Resistance Mechanisms
- Neonatal Respiratory Health Research
- Inhalation and Respiratory Drug Delivery
- Systemic Lupus Erythematosus Research
- Erythrocyte Function and Pathophysiology
- Renal Diseases and Glomerulopathies
- Bacterial Infections and Vaccines
- S100 Proteins and Annexins
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
- Pluripotent Stem Cells Research
- Tuberculosis Research and Epidemiology
- Reproductive System and Pregnancy
- Peripheral Neuropathies and Disorders
- COVID-19 Impact on Reproduction
The University of Texas Health Science Center at Houston
2013-2024
Brown Foundation
2012-2023
The University of Texas at Austin
2006-2013
University of Tennessee Health Science Center
2011
Institute for Molecular Medicine
2000-2008
Institute of Molecular Medicine
1997-2007
University of Pennsylvania
2006
University of Michigan–Ann Arbor
2004
Medizinische Hochschule Hannover
2004
Canadian Blood Services
2003
Antiphospholipid syndrome (APS) is defined by recurrent pregnancy loss and thrombosis in the presence of antiphospholipid (aPL) Ab’s. Currently, therapy for pregnant women with APS focused on preventing thrombosis, but anticoagulation only partially successful averting miscarriage. We hypothesized that complement activation a central mechanism tested this model which mice receive human IgG containing aPL Here we identify component C5 (and particularly its cleavage product C5a) neutrophils as...
Antiphospholipid syndrome (APS) is defined by recurrent pregnancy loss and thrombosis in the presence of antiphospholipid (aPL) Ab's. Currently, therapy for pregnant women with APS focused on preventing thrombosis, but anticoagulation only partially successful averting miscarriage. We hypothesized that complement activation a central mechanism tested this model which mice receive human IgG containing aPL Here we identify component C5 (and particularly its cleavage product C5a) neutrophils as...
Abstract The small-complement C5 activation fragment, C5a, is a potent phlogistic molecule that, on binding to the C5a Receptor (C5aR), mediates contraction of smooth muscle, enhances vascular permeability, and promotes leukocyte functions such as directed chemotaxis, degranulation, mediator release, production superoxide anions. Although C5aR expression has traditionally been thought be limited primarily myeloid blood cells, including neutrophils, monocytes, macrophages, eosinophils, we...
Alveolar epithelial type II (ATII) cells are small, cuboidal that constitute approximately 60% of the pulmonary alveolar epithelium. These crucial for repair injured alveolus by differentiating into I cells. ATII derived from human ES (hES) a promising source could be used therapeutically to treat distal lung diseases. We have developed reliable transfection and culture procedure, which facilitates, via genetic selection, differentiation hES an essentially pure (>99%) population (hES-ATII)....
The expression of chemotactic receptors in the central nervous system is largely unexplored.In this study, we examined human astrocytes and microglia as well conditionally immortalized astrocyte cell line HSC2 for CSa-anaphylatoxin receptor (CSaR), interleukin-8 (IL-8R) f-Met-Leu-Phe (FMLPR).Using flow cytometry, indirect immunofluorescence RT-PCR analysis, demonstrated that astrocytes, cells contain specific RNA express surface protein all three receptors.These are first studies to...
Abstract The presence of the complement-derived anaphylatoxin peptides, C3a and C5a, in lung can induce respiratory distress characterized by contraction smooth muscle walls bronchioles pulmonary arteries aggregation platelets leukocytes vessels. C5a mediate these effects binding to their specific receptors, C3aR C5aR, respectively. cells that express receptors have not been thoroughly investigated, nor has expression examined during inflammation. Accordingly, C5aR normal human murine was...
Abstract In systemic lupus erythematosus, the renal deposition of complement-containing immune complexes initiates an inflammatory cascade resulting in glomerulonephritis. Activation classical complement pathway with C3 is pathogenic nephritis. Although alternative activated nephritis, its role disease pathogenesis unknown. To determine factor B-deficient mice were backcrossed to MRL/lpr mice. develop a spontaneous lupus-like characterized by complex We derived B wild-type (B+/+), homozygous...
To ascertain the molecular mechanism that causes murine C5 deficiency, genomic and cDNA libraries were constructed from mouse liver DNA mRNA employing congenic strains B10.D2/nSnJ B10.D2/oSnJ are sufficient deficient for C5, respectively. Genomic fragments isolated which correspond to PvuII HindIII restriction fragment length polymorphisms associated with deficiency. Sequence analyses demonstrated each of these resulted single base pair substitutions neither substitution would probably cause...
A comparison of the sequence subunit human alpha 2-macroglobulin (alpha 2M; 1451 amino acid residues) with that murine complement component pro-C3 (1639 reveals eight extended regions similarity. These contain between 19% and 31% identically placed residues account for 75% 67%, respectively, polypeptide chains 2M pro-C3. Published data C4 show segments this protein match well corresponding stretches in It is proposed 2M, C3 C4, which all a unique activatable beta-cysteinyl-gamma-glutamyl...
Abstract Although the complement system has been implicated in liver regeneration after toxic injury and partial hepatectomy, mechanism or mechanisms through which it participates these processes remains ill-defined. In this study, we demonstrate that activation products (C3a, C3b/iC3b) are generated serum of experimental mice CCl4 injection is required for normal regeneration. Decomplementation by cobra venom factor resulted impaired entry hepatocytes into S phase cell cycle. addition,...
Abstract Human embryonic stem cells (hESCs) are a promising source of for tissue regeneration, yet histoincompatibility remains major challenge to their clinical application. Because the human leukocyte antigen class I (HLA-I) molecules primary mediators immune rejection, we hypothesized that derived from hESC line lacking HLA-I expression could be transplanted without evoking robust response allogeneic recipients. In present study, used replacement targeting strategy delete exons 2 and 3...
C3a is a key complement activation fragment, yet its neutrophil-expressed receptor (C3aR) still has no clearly defined role. In this study, we used neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to explore the role C3aR in acute tissue injuries. deficiency worsened injury, which corresponded with increased numbers tissue-infiltrating neutrophils. Circulating neutrophils were significantly −/− mice after ischemia, and also mobilized more circulating...
Respiratory diseases are a major cause of mortality and morbidity worldwide. Current treatments offer no prospect cure or disease reversal. Transplantation pulmonary progenitor cells derived from human embryonic stem (hESCs) may provide novel approach to regenerate endogenous lung destroyed by injury disease. Here, we examine the therapeutic potential alveolar type II epithelial hESCs (hES-ATIICs) in mouse model acute injury. When transplanted into lungs mice subjected bleomycin...
Abstract The complement system, especially the alternative pathway, plays essential roles in induction of injury collagen Ab-induced arthritis (CAIA) mice. goal current study was to directly compare receptors for C3a and C5a, as well membrane attack complex, effector mechanisms pathogenesis CAIA. Clinical disease activity C3aR−/−, C5aR−/−, C6-deficient (C6-def) mice decreased by 52, 94, 65%, respectively, compared with wild-type Decreases histopathologic IgG C3 deposition paralleled clinical...
Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells extensive rewiring the remaining connections, yet about 50% survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in subacute chronic phase after ischaemic stroke. We previously showed complement-derived peptide C3a regulates progenitor cell migration vitro receptor signalling stimulates...
The sequelae of diabetes include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury associated with a disruption in mitochondrial metabolic agility, inflammation, and fibrosis. We explored the role innate immune complement component C5a, potent mediator pathogenesis DKD clinical experimental diabetes. Marked systemic elevation C5a activity was demonstrated patients diabetes; conventional renoprotective agents did not...
Abstract The complement anaphylatoxin C3a, on binding the C3aR, mediates numerous proinflammatory activities. In addition, recent in vitro studies with C3a have implicated C3aR as a possible anti-inflammatory receptor. Because of its dual role modulating inflammatory response, it is uncertain whether contributes to pathogenesis endotoxin shock. Here, targeted-disruption mice reported. These exhibit an enhanced lethality shock pronounced gene dosage effect. plasma concentration IL-1β was...
Experimental sepsis in rodents occurring after cecal ligation/puncture (CLP) is associated with excessive complement activation and a systemic inflammatory response. The proinflammatory mediator IL-6 has recently been shown to be an important inducer of the C5a receptor (C5aR) during sepsis. We now provide evidence that serum production rats was reduced neutrophil-depleted animals absence C5aR mice as well antibody-blockade significantly levels Lipopolysaccharide (LPS)-induced vitro by...
Abstract Asthma is a chronic inflammatory disease of the lung resulting in airway obstruction. The inflammation asthma strongly linked to Th2 lymphocytes and their cytokines, particularly IL-4, IL-5, IL-13, which regulate hyperresponsiveness, eosinophil activation, mucus production, IgE secretion. Historically, complement was not thought contribute pathogenesis asthma. However, our previous reports have demonstrated that contributes bronchial hyperreactivity, recruitment eosinophils, IL-4...