Go to JCI Insight
Jci spelled out white on transparent.20160208
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Biology of familial cancer predisposition syndromes (Feb 2019)
    • Mitochondrial dysfunction in disease (Aug 2018)
    • Lipid mediators of disease (Jul 2018)
    • Cellular senescence in human disease (Apr 2018)
    • Fibrosis (Jan 2018)
    • Glia and Neurodegeneration (Sep 2017)
    • Transplantation (Jun 2017)
    • View all review series...
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Scientific Show Stoppers
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

Jci only white

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication

Cell biology

  • 139 Articles
  • 0 Posts
  • ←
  • 1
  • 2
  • …
  • 12
  • 13
  • 14
  • →
Bone marrow–derived progenitor cells in pulmonary fibrosis
Naozumi Hashimoto, … , Stephen W. Chensue, Sem H. Phan
Naozumi Hashimoto, … , Stephen W. Chensue, Sem H. Phan
Published January 15, 2004
Citation Information: J Clin Invest. 2004;113(2):243-252. https://doi.org/10.1172/JCI18847.
View: Text | PDF

Bone marrow–derived progenitor cells in pulmonary fibrosis

  • Text
  • PDF
Abstract

The origin of fibroblasts in pulmonary fibrosis is assumed to be intrapulmonary, but their extrapulmonary origin and especially derivation from bone marrow (BM) progenitor cells has not been ruled out. To examine this possibility directly, adult mice were durably engrafted with BM isolated from transgenic mice expressing enhanced GFP. Induction of pulmonary fibrosis in such chimera mice by endotracheal bleomycin (BLM) injection caused large numbers of GFP+ cells to appear in active fibrotic lesions, while only a few GFP+ cells could be identified in control lungs. Flow-cytometric analysis of lung cells confirmed the BLM-induced increase in GFP+ cells in chimera mice and revealed a significant increase in GFP+ cells that also express type I collagen. GFP+ lung fibroblasts isolated from chimera mice expressed collagen and telomerase reverse transcriptase but not α-smooth muscle actin. Treatment of isolated GFP+ fibroblasts with TGF-β failed to induce myofibroblast differentiation. Cultured lung fibroblasts expressed the chemokine receptors CXCR4 and CCR7 and responded chemotactically to their cognate ligands, stromal cell–derived factor-1α and secondary lymphoid chemokine, respectively. Thus the collagen-producing lung fibroblasts in pulmonary fibrosis can also be derived from BM progenitor cells.

Authors

Naozumi Hashimoto, Hong Jin, Tianju Liu, Stephen W. Chensue, Sem H. Phan

×

Hyperosmolarity enhances the lung capillary barrier
Zeenat Safdar, … , Sadiqa Quadri, Jahar Bhattacharya
Zeenat Safdar, … , Sadiqa Quadri, Jahar Bhattacharya
Published November 15, 2003
Citation Information: J Clin Invest. 2003;112(10):1541-1549. https://doi.org/10.1172/JCI18370.
View: Text | PDF

Hyperosmolarity enhances the lung capillary barrier

  • Text
  • PDF
Abstract

Although capillary barrier deterioration underlies major inflammatory lung pathology, barrier-enhancing strategies are not available. To consider hyperosmolar therapy as a possible strategy, we gave 15-minute infusions of hyperosmolar sucrose in lung venular capillaries imaged in real time. Surprisingly, this treatment enhanced the capillary barrier, as indicated by quantification of the capillary hydraulic conductivity. The barrier enhancement was sufficient to block the injurious effects of thrombin, TNF-α, and H2O2 in single capillaries, and of intratracheal acid instillation in the whole lung. Capillary immunofluorescence indicated that the hyperosmolar infusion markedly augmented actin filament formation and E-cadherin expression at the endothelial cell periphery. The actin-depolymerizing agent latrunculin B abrogated the hyperosmolar barrier enhancement as well as the actin filament formation, suggesting a role for actin in the barrier response. Furthermore, hyperosmolar infusion blocked TNF-α–induced P-selectin expression in an actin-dependent manner. Our results provide the first evidence to our knowledge that in lung capillaries, hyperosmolarity remodels the endothelial barrier and the actin cytoskeleton to enhance barrier properties and block proinflammatory secretory processes. Hyperosmolar therapy may be beneficial in lung inflammatory disease.

Authors

Zeenat Safdar, Ping Wang, Hideo Ichimura, Andrew C. Issekutz, Sadiqa Quadri, Jahar Bhattacharya

×

Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ
L. Chastine Bell-Parikh, … , Muredach Reilly, Garret A. FitzGerald
L. Chastine Bell-Parikh, … , Muredach Reilly, Garret A. FitzGerald
Published September 15, 2003
Citation Information: J Clin Invest. 2003;112(6):945-955. https://doi.org/10.1172/JCI18012.
View: Text | PDF

Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ

  • Text
  • PDF
Abstract

15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) has been identified as an endogenous ligand for PPARγ, inducing adipogenesis in vitro. Additional roles for this molecule in the propagation and resolution of inflammation, ligation of NF-κB, and mediation of apoptosis have been proposed. However, quantitative, physiochemical evidence for the formation of 15d-PGJ2 in vivo is lacking. We report that 15d-PGJ2 is detectable using liquid chromatography–mass spectrometry–mass spectrometry at low picomolar concentrations in the medium of 3T3-L1 preadipocytes. However, despite induction of COX-2, production of PGs, including 15d-PGJ2, does not increase during adipocyte differentiation, a process unaltered by COX inhibition. 15d-PGJ2 is detectable as a minor product of COX-2 in human urine. However, its biosynthesis is unaltered during or after COX activation in vivo by LPS. Furthermore, the biosynthesis of 15d-PGJ2 is not augmented in the joint fluid of patients with arthritis, nor is its urinary excretion increased in patients with diabetes or obesity. 15d-PGJ2 is not the endogenous mediator of PPARγ-dependent adipocyte activation and is unaltered in clinical settings in which PPARγ activation has been implicated.

Authors

L. Chastine Bell-Parikh, Tomomi Ide, John A. Lawson, Peter McNamara, Muredach Reilly, Garret A. FitzGerald

×

Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension
Ventzislav Petkov, … , Bernhard Burian, Lutz-Henning Block
Ventzislav Petkov, … , Bernhard Burian, Lutz-Henning Block
Published May 1, 2003
Citation Information: J Clin Invest. 2003;111(9):1339-1346. https://doi.org/10.1172/JCI17500.
View: Text | PDF

Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension

  • Text
  • PDF
Abstract

Primary pulmonary hypertension is a fatal disease causing progressive right heart failure within 3 years after diagnosis. We describe a new concept for treatment of the disease using vasoactive intestinal peptide, a neuropeptide primarily functioning as a neurotransmitter that acts as a potent systemic and pulmonary vasodilator. Our rationale is based on the finding of a deficiency of the peptide in serum and lung tissue of patients with primary pulmonary hypertension, as evidenced by radioimmunoassay and immunohistochemistry. The relevance of this finding is underlined by an upregulation of corresponding receptor sites as shown by Northern blot analysis, Western blot analysis, and immunological techniques. Consequently, the substitution with the hormone results in substantial improvement of hemodynamic and prognostic parameters of the disease without side effects. It decreased the mean pulmonary artery pressure in our eight study patients, increased cardiac output, and mixed venous oxygen saturation. Our data provide enough proof for further investigation of vasoactive intestinal peptide and its role in primary pulmonary hypertension.

Authors

Ventzislav Petkov, Wilhelm Mosgoeller, Rolf Ziesche, Markus Raderer, Leopold Stiebellehner, Karin Vonbank, Georg-Christian Funk, Gerhard Hamilton, Clemens Novotny, Bernhard Burian, Lutz-Henning Block

×

DNA damage is a novel response to sublytic complement C5b-9–induced injury in podocytes
Jeffrey W. Pippin, … , William G. Couser, Stuart J. Shankland
Jeffrey W. Pippin, … , William G. Couser, Stuart J. Shankland
Published March 15, 2003
Citation Information: J Clin Invest. 2003;111(6):877-885. https://doi.org/10.1172/JCI15645.
View: Text | PDF

DNA damage is a novel response to sublytic complement C5b-9–induced injury in podocytes

  • Text
  • PDF
Abstract

In response to Ab-complement–mediated injury, podocytes can undergo lysis, apoptosis, or, when exposed to sublytic (<5% lysis) amounts of C5b-9, become activated. Following the insertion of sublytic quantities of C5b-9, there is an increase in signaling pathways and growth factor synthesis and release of proteases, oxidants, and other molecules. Despite an increase in DNA synthesis, however, sublytic C5b-9 is associated with a delay in G2/M phase progression in podocytes. Here we induced sublytic C5b-9 injury in vitro by exposing cultured rat podocytes or differentiated postmitotic mouse podocytes to Ab and a complement source; we also studied the passive Heymann nephritis model of experimental membranous nephropathy in rats. A major finding was that sublytic C5b-9–induced injury caused an increase in DNA damage in podocytes both in vitro and in vivo. This was associated with an increase in protein levels for p53, the CDK inhibitor p21, growth-arrest DNA damage-45 (GADD45), and the checkpoint kinases-1 and -2. Sublytic C5b-9 increased extracellular signal-regulated kinase-1 and -2 (ERK-1 and -2), and inhibiting ERK-1 and -2 reduced the increase in p21 and GADD45 and augmented the DNA damage response to sublytic C5b-9–induced injury. These results show that sublytic C5b-9 induces DNA damage in vitro and in vivo and may explain why podocyte proliferation is limited following immune-mediated injury.

Authors

Jeffrey W. Pippin, Raghu Durvasula, Arndt Petermann, Keiju Hiromura, William G. Couser, Stuart J. Shankland

×

CD44 is a macrophage binding site for Mycobacterium tuberculosis that mediates macrophage recruitment and protective immunity against tuberculosis
Jaklien C. Leemans, … , Ronald van der Neut, Tom van der Poll
Jaklien C. Leemans, … , Ronald van der Neut, Tom van der Poll
Published March 1, 2003
Citation Information: J Clin Invest. 2003;111(5):681-689. https://doi.org/10.1172/JCI16936.
View: Text | PDF

CD44 is a macrophage binding site for Mycobacterium tuberculosis that mediates macrophage recruitment and protective immunity against tuberculosis

  • Text
  • PDF
Abstract

Cell migration and phagocytosis are both important for controlling Mycobacterium tuberculosis infection and are critically dependent on the reorganization of the cytoskeleton. Since CD44 is an adhesion molecule involved in inflammatory responses and is connected to the actin cytoskeleton, we investigated the role of CD44 in both these processes. Macrophage (Mφ) recruitment into M. tuberculosis–infected lungs and delayed-type hypersensitivity sites was impaired in CD44-deficient (CD44–/–) mice. In addition, the number of T lymphocytes and the concentration of the protective key cytokine IFN-γ were reduced in the lungs of infected CD44–/– mice. The production of IFN-γ by splenocytes of CD44–/– mice was profoundly increased upon antigen-specific stimulation. Flow cytometry analysis revealed that soluble CD44 can directly bind to virulent M. tuberculosis. Mycobacteria also interacted with Mφ-associated CD44, as reflected by reduced binding and internalization of bacilli by CD44–/– Mφs. This suggests that CD44 is a receptor on Mφs for binding of M. tuberculosis. CD44–/– mice displayed a decreased survival and an enhanced mycobacterial outgrowth in lungs and liver during pulmonary tuberculosis. In summary, we have identified CD44 as a new Mφ binding site for M. tuberculosis that mediates mycobacterial phagocytosis, Mφ recruitment, and protective immunity against pulmonary tuberculosis.

Authors

Jaklien C. Leemans, Sandrine Florquin, Mirjam Heikens, Steven T. Pals, Ronald van der Neut, Tom van der Poll

×

Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils
Andrei L. Kindzelskii, … , Roberto Romero, Howard R. Petty
Andrei L. Kindzelskii, … , Roberto Romero, Howard R. Petty
Published December 15, 2002
Citation Information: J Clin Invest. 2002;110(12):1801-1811. https://doi.org/10.1172/JCI15973.
View: Text | PDF

Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils

  • Text
  • PDF
Abstract

Research Article

Authors

Andrei L. Kindzelskii, Ji-Biao Huang, Tinnakorn Chaiworapongsa, Ryan M. Fahmy, Yeon Mee Kim, Roberto Romero, Howard R. Petty

×

P311 induces a TGF-β1–independent, nonfibrogenic myofibroblast phenotype
Desi Pan, … , Gregory A. Taylor, Lucia Schuger
Desi Pan, … , Gregory A. Taylor, Lucia Schuger
Published November 1, 2002
Citation Information: J Clin Invest. 2002;110(9):1349-1358. https://doi.org/10.1172/JCI15614.
View: Text | PDF

P311 induces a TGF-β1–independent, nonfibrogenic myofibroblast phenotype

  • Text
  • PDF
Abstract

Research Article

Authors

Desi Pan, Xiaoning Zhe, Sandhya Jakkaraju, Gregory A. Taylor, Lucia Schuger

×

Neutrophil-independent mechanisms of caspase-1– and IL-18–mediated ischemic acute tubular necrosis in mice
Vyacheslav Y. Melnikov, … , Danica Ljubanovic, Charles L. Edelstein
Vyacheslav Y. Melnikov, … , Danica Ljubanovic, Charles L. Edelstein
Published October 15, 2002
Citation Information: J Clin Invest. 2002;110(8):1083-1091. https://doi.org/10.1172/JCI15623.
View: Text | PDF

Neutrophil-independent mechanisms of caspase-1– and IL-18–mediated ischemic acute tubular necrosis in mice

  • Text
  • PDF
Abstract

Research Article

Authors

Vyacheslav Y. Melnikov, Sarah Faubel, Britta Siegmund, M. Scott Lucia, Danica Ljubanovic, Charles L. Edelstein

×
  • ←
  • 1
  • 2
  • …
  • 12
  • 13
  • 14
  • →

No posts were found with this tag.

Advertisement
Follow JCI: Facebook logo white Twitter logo v2 Rss icon
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts