A5004554046- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Platelet Disorders and Treatments
- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Systemic Lupus Erythematosus Research
- Angiogenesis and VEGF in Cancer
- Blood Coagulation and Thrombosis Mechanisms
- Chronic Kidney Disease and Diabetes
- Inflammasome and immune disorders
- Immune cells in cancer
- S100 Proteins and Annexins
- Chemokine receptors and signaling
- Acute Kidney Injury Research
- Atherosclerosis and Cardiovascular Diseases
- Mast cells and histamine
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Immune responses and vaccinations
- Renal and Vascular Pathologies
Harvard University
2011-2022
Brigham and Women's Hospital
2012-2022
University of Alberta
2015
Fundación Santa Fe de Bogotá
2015
Universidad de Los Andes
2015
Universidad Nacional de Colombia
2015
Massachusetts General Hospital
2015
Boston University
2015
Center for Vascular Biology Research
2012
Harvard University Press
1996-2009
Levels of proinflammatory cytokines associate with risk for developing type 2 diabetes but whether chronic inflammation contributes to the development diabetic complications, such as ESRD, is unknown. In 1990s, we recruited 410 patients studies nephropathy and recorded their characteristics at enrollment. During 12 years follow-up, 59 developed ESRD (17 per 1000 patient-years) 84 died without (24 patient-years). Plasma markers systemic inflammation, endothelial dysfunction, TNF pathway were...
Elevated plasma concentrations of TNF receptors 1 and 2 (TNFR1 TNFR2) predict development ESRD in patients with type diabetes without proteinuria, suggesting these markers may contribute to the pathogenesis renal decline. We investigated whether circulating pathway determine GFR loss among diabetes. followed two cohorts comprising 628 diabetes, normal function, no proteinuria. Over 12 years, 69 developed estimated less than 60 mL/min per 1.73 m2 (16 1000 person-years). Concentrations TNFR1...
The period of hypoxia is an important priming event for the vascular dysfunction that accompanies reperfusion, with endothelial cells (ECs) and neutrophils (PMNs) playing a central role. We hypothesized EC Weibel-Palade (WP) body exocytosis during hypoxic/ischemic organ preservation permits brisk PMN recruitment into postischemic tissue, process further amplified in oxidant-rich milieu. Exposure human umbilical vein ECs to hypoxic environment (pO2 approximately 20 torr) stimulated release...
P-selectin is expressed on activated endothelium and platelets where it can bind monocytes, neutrophils, stimulated T cells, platelets. Because recruitment of these cells critical for atherosclerotic lesion development, we examined whether might play a role in atherosclerosis. We intercrossed P-selectin-deficient mice with lacking the low density lipoprotein receptor (LDLR) because readily develop lesions diets rich saturated fat cholesterol. The atherogenic diet leukocyte rolling mesenteric...
Macrophage-1 antigen (Mac-1) (CD11b/CD18), a leukocyte beta2 integrin, facilitates neutrophil adhesion, transendothelial migration, phagocytosis, and respiratory burst, all of which may mediate reperfusion-induced injury to ischemic brain tissue in conditions such as stroke. To determine the role Mac-1 during ischemia reperfusion brain, we analyzed effect transient focal cerebral mice genetically engineered with specific deficiency Mac-1.Transient ischemia/reperfusion was induced by...
Mac-1 (αmβ2), a leukocyte adhesion receptor, has been shown in vitro to functionally interact with Fcγ receptors facilitate immune complex (IC)–stimulated polymorphonuclear neutrophil (PMN) functions. To investigate the relevance of Mac-1–FcγR interactions IC-mediated injury vivo, we induced model Fc-dependent anti–glomerular basement membrane (GBM) nephritis wild-type and Mac-1–deficient mice by intravenous injection anti-GBM antibody. The initial glomerular PMN accumulation was equivalent...
Abstract Receptors for human immunoglobulin (Ig)G and IgA initiate potent cytolysis of antibody (Ab)-coated targets by polymorphonuclear leukocytes (PMNs). Mac-1 (complement receptor type 3, CD11b/CD18) has previously been implicated in cooperation with Fc receptors (FcRs). The role FcR-mediated lysis tumor cells was characterized studying normal PMNs, Mac-1–deficient mouse PMNs transgenic FcR. All efficiently phagocytosed Ab-coated particles. However, antibody-dependent cellular...
Two conditions were identified that interfered with the complex polymerization process in biosynthesis of von Willebrand factor (vWf). Treatment human umbilical vein endothelial cells tunicamycin inhibited N-linked glycosylation nascent vWf and resulting pro-vWf monomers failed to dimerize. The single subunits accumulated endoplasmic reticulum neither processed further nor secreted. In presence a weak base (ammonium chloride or chloroquine), interdimer disulfide bond formation was...
Vascular endothelium is a dynamic cellular interface that displays unique phenotypic plasticity. This plasticity critical for vascular function and when dysregulated pathogenic in several diseases. Human genotype-phenotype studies of are limited by the unavailability patient-specific endothelial cells. To establish platform studying biology, we have generated from human induced pluripotent stem cells (iPSCs) exhibiting rich functional mature primary endothelium. These respond to diverse...
Complement components and their receptors are found within around amyloid β (Aβ) cerebral plaques in Alzheimer's disease (AD). Microglia defend against pathogens through phagocytosis via complement component C3 and/or engagement of cleavage product iC3b with receptor type 3 (CR3, Mac-1). Here, we provide direct evidence that Mac-1 mediate, part, clearance fibrillar amyloid-β (fAβ) by murine microglia vitro vivo. took up not only synthetic fAβ(42) but also cores from patients AD, transporting...
Abstract Inflammasomes are central mediators of host defense to a wide range microbial pathogens. The nucleotide-binding domain and leucine-rich repeat containing family (NLR), pyrin domain–containing 3 (NLRP3) inflammasome plays key role in triggering caspase-1–dependent IL-1β maturation resistance fungal dissemination Candida albicans infection. β-Glucans major components cell walls that trigger secretion both murine human immune cells. In this study, we sought determine the contribution...