The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system.

Abstract:

:The human cathelicidin LL-37 is a cationic host defense peptide (antimicrobial peptide) expressed primarily by neutrophils and epithelial cells. This peptide, up-regulated under conditions of inflammation, has immunomodulatory and antimicrobial functions. We demonstrate that LL-37 is a potent inhibitor of human neutrophil apoptosis, signaling through P2X(7) receptors and G-protein-coupled receptors other than the formyl peptide receptor-like-1 molecule. This process involved modulation of Mcl-1 expression, inhibition of BID and procaspase-3 cleavage, and the activation of phosphatidylinositol-3 kinase but not the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway. In contrast to the inhibition of neutrophil apoptosis, LL-37 induced apoptosis in primary airway epithelial cells, demonstrating alternate consequences of LL-37-mediated modulation of apoptotic pathways in different human primary cells. We propose that these novel immunomodulatory properties of LL-37 contribute to peptide-mediated enhancement of innate host defenses against acute infection and are of considerable significance in the development of such peptides and their synthetic analogs as potential therapeutics for use against multiple antibiotic-resistant infectious diseases.

journal_name

J Leukoc Biol

authors

Barlow PG,Li Y,Wilkinson TS,Bowdish DM,Lau YE,Cosseau C,Haslett C,Simpson AJ,Hancock RE,Davidson DJ

doi

10.1189/jlb.1005560

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

509-20

issue

3

eissn

0741-5400

issn

1938-3673

pii

jlb.1005560

journal_volume

80

pub_type

杂志文章
  • Regulatory B cells and advances in transplantation.

    abstract::The effects of B cell subsets with regulatory activity on the immune response to an allograft have evoked increasing interest. Here, we summarize the function and signaling of regulatory B cells (Bregs) and their potential effects on transplantation. These cells are able to suppress the immune system directly via liga...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/JLB.5RU0518-199R

    authors: Li J,Luo Y,Wang X,Feng G

    更新日期:2019-04-01 00:00:00

  • PI3Kγ controls leukocyte recruitment, tissue injury, and lethality in a model of graft-versus-host disease in mice.

    abstract::PI(3)Kγ is thought to mediate leukocyte migration to injured tissues and may be important in the pathogenesis of various T-lymphocyte-dependent pathologies, including autoimmune and inflammatory diseases. The present study evaluated the relevance of PI(3)Kγ in donor cells for the pathogenesis of acute GVHD using a mod...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0810464

    authors: Castor MG,Rezende BM,Bernardes PT,Vieira AT,Vieira EL,Arantes RM,Souza DG,Silva TA,Teixeira MM,Pinho V

    更新日期:2011-06-01 00:00:00

  • Development, differentiation, and maturation of macrophages in the fetal mouse liver.

    abstract::Primitive macrophages emerged in the sinusoidal lumen of the fetal mouse liver at 10 days of gestation before the initiation of hepatic hematopoiesis and matured into fetal macrophages. In the culture of cell suspensions from the fetal liver with LP3-conditioned medium, monocyte colonies were formed, but monocytopoies...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.48.1.27

    authors: Naito M,Takahashi K,Nishikawa S

    更新日期:1990-07-01 00:00:00

  • Loss of response to beta-adrenoceptor agonists during the maturation of human monocytes to macrophages in vitro.

    abstract::We have previously reported that human airway macrophages do not respond to the beta-adrenoceptor agonist isoprenaline. The airway macrophage is known to be derived from the blood monocyte. In this study we have assessed the effect of beta-adrenoceptor stimulation on human monocytes matured into macrophages in vitro, ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.57.3.395

    authors: Baker AJ,Fuller RW

    更新日期:1995-03-01 00:00:00

  • A direct signaling pathway through tyrosine kinase activation of SH2 domain-containing transcription factors.

    abstract::Studies on the mechanism of interferon-induced gene expression revealed a direct signaling pathway from cell surface receptors to transcription factors. In this pathway, signal transduction is mediated by a new class of transcription factor STAT (signal transducer and activator of transcription). We have shown that ST...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/jlb.57.4.529

    authors: Fu XY

    更新日期:1995-04-01 00:00:00

  • Characterization of thyroid fibrosis in a murine model of granulomatous experimental autoimmune thyroiditis.

    abstract::This study was initiated to identify and characterize thyroid fibrosis in a murine model of granulomatous experimental autoimmune thyroiditis (G-EAT) and determine if TGF-beta1 might be involved in fibrosis. G-EAT was induced by transfer of mouse thyroglobulin-sensitized spleen cells activated in vitro with thyroglobu...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Chen K,Wei Y,Sharp GC,Braley-Mullen H

    更新日期:2000-12-01 00:00:00

  • Monocyte/macrophage traffic in HIV and SIV encephalitis.

    abstract::This short review focuses on the role of central nervous system (CNS) perivascular macrophages as targets of productive infection of the CNS. Data discussed include the importance of these cells as early targets of infection and their productive infection with AIDS. Many of the immune molecules on perivascular macroph...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0503207

    authors: Kim WK,Corey S,Alvarez X,Williams K

    更新日期:2003-11-01 00:00:00

  • Targeted STAT3 disruption in myeloid cells alters immunosuppressor cell abundance in a murine model of spontaneous medulloblastoma.

    abstract::Although the immune system may provide early protection against cancer, tumors may exploit the healing arm of the immune system to enhance their growth and metastasis. For example, myeloid derived suppressor cells (MDSCs) are thought to promote tumor growth by several mechanisms, including the suppression of T cell ac...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1012531

    authors: Abad C,Nobuta H,Li J,Kasai A,Yong WH,Waschek JA

    更新日期:2014-02-01 00:00:00

  • The glutamate-glutamine cycle as an inducible, protective face of macrophage activation.

    abstract::Neuronal damage in HIV infection results mainly from chronic activation of brain tissue and involves inflammation, oxidative stress, and glutamate-related neurotoxicity. Glutamate toxicity acts via two distinct pathways: an excitotoxic one, in which glutamate receptors are hyperactivated, and an oxidative one, in whic...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0306153

    authors: Gras G,Porcheray F,Samah B,Leone C

    更新日期:2006-11-01 00:00:00

  • MC148 encoded by human molluscum contagiosum poxvirus is an antagonist for human but not murine CCR8.

    abstract::The viral CC chemokines MC148, encoded by the poxvirus molluscum contagiosum, and viral macrophage inflammatory protein (vMIP)-I and vMIP-II, encoded by human herpesvirus 8, were probed on the murine CC receptor (CCR) 8 in parallel with human CCR8. In calcium mobilization assays, vMIP-I acted as a high-affinity agonis...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Lüttichau HR,Gerstoft J,Schwartz TW

    更新日期:2001-08-01 00:00:00

  • Immobilization of rolling NK cells on platelet-borne P-selectin under flow by proinflammatory stimuli, interleukin-12, and leukotriene B4.

    abstract::Recruitment of leukocytes from bloodstream to extrahematic sites is tightly regulated by a variety of adhesion molecules that are expressed on the leukocytes and the vessel walls. In this manuscript, we describe the interactions between natural killer (NK) cells and activated, autologous platelets under physiologic fl...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0204106

    authors: Sheikh S,Parhar RS,Bakheet R,Saleh S,Collison K,Al-Mohanna F

    更新日期:2004-09-01 00:00:00

  • Antimicrobial zinc toxicity in Mϕs: ZnT1 pays the toll.

    abstract::Transition metals, including zinc, are essential to all living organisms. They are also toxic in high amounts, and their intracellular concentration must be tightly regulated. In this edition of JLB, Stocks et al. report that the zinc transporter, ZnT1 (SLC30A1) is induced by TLR4 activation in Mϕs, in which it contri...

    journal_title:Journal of leukocyte biology

    pub_type: 社论

    doi:10.1002/JLB.4CE0520-256R

    authors: Neyrolles O

    更新日期:2021-02-01 00:00:00

  • Actin cytoskeletal dynamics in T lymphocyte activation and migration.

    abstract::Dynamic rearrangements of the actin cytoskeleton are crucial for the function of numerous cellular elements including T lymphocytes. They are required for migration of T lymphocytes through the body to scan for the presence of antigens, as well as for the formation and stabilization of the immunological synapse at the...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0602272

    authors: Samstag Y,Eibert SM,Klemke M,Wabnitz GH

    更新日期:2003-01-01 00:00:00

  • Induction of cyclooxygenase-2 by human monocytes exposed to group B streptococci.

    abstract::Group B streptococcal (GBS) infections are associated with high morbidity and mortality. The molecular pathways mediating the pathophysiological events in GBS infection are not fully delineated. Cyclooxygenases (COX) are the enzymes that convert arachidonate to active eicosanoids. To identify the effects of GBS on eic...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.67.5.615

    authors: Maloney CG,Thompson SD,Hill HR,Bohnsack JF,McIntyre TM,Zimmerman GA

    更新日期:2000-05-01 00:00:00

  • Donor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease.

    abstract::IL-10 is a key immune-regulatory cytokine, and its gene polymorphisms correlate with severity of clinical GVHD. IL-10 is made by a variety of donor and host cells, but the functional relevance of its source and its role in the biology of acute GVHD are not well understood. We used preclinical models to examine the rel...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1011510

    authors: Tawara I,Sun Y,Liu C,Toubai T,Nieves E,Evers R,Alrubaie M,Mathewson N,Tamaki H,Reddy P

    更新日期:2012-04-01 00:00:00

  • Respiratory viral infection, epithelial cytokines, and innate lymphoid cells in asthma exacerbations.

    abstract::Exacerbations of asthma are most commonly triggered by viral infections, which amplify allergic inflammation. Cytokines released by virus-infected AECs may be important in driving this response. This review focuses on accumulating evidence in support of a role for epithelial cytokines, including IL-33, IL-25, and TSLP...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.3RI0314-129R

    authors: Kumar RK,Foster PS,Rosenberg HF

    更新日期:2014-09-01 00:00:00

  • Alcohol abuse and pulmonary disease.

    abstract::ARDS is a severe form of lung injury characterized by increased permeability of the alveolar capillary membrane, diffuse alveolar damage, the accumulation of proteinaceous interstitial and intra-alveolar edema, and the presence of hyaline membranes. These pathological changes are accompanied by physiological alteratio...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0209087

    authors: Boé DM,Vandivier RW,Burnham EL,Moss M

    更新日期:2009-11-01 00:00:00

  • Impacts of HIV infection on Vgamma2Vdelta2 T cell phenotype and function: a mechanism for reduced tumor immunity in AIDS.

    abstract::HIV infection causes rapid and lasting defects in the population of Vgamma2Vdelta2 T cells. To fully describe the impact of HIV, we examined PBMC samples from HIV+ patients receiving highly active antiretroviral therapy, who had displayed prolonged viral control and CD4 counts above 300 cells/mm3. We observed lower fr...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1207847

    authors: Cummings JS,Cairo C,Armstrong C,Davis CE,Pauza CD

    更新日期:2008-08-01 00:00:00

  • Monocytic myeloid-derived suppressor cells reflect tuberculosis severity and are influenced by cyclooxygenase-2 inhibitors.

    abstract::Myeloid-derived suppressor cells (MDSCs) increase in tuberculosis (TB) and may be targets for host-directed therapy (HDT). In this study, we use flow cytometry to analyze the effects of cyclooxygenase-2 inhibitors (COX-2i) on monocytic (M)-MDSCs in blood from TB patients attending a clinical trial of COX-2i. The effec...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/JLB.4A0720-409RR

    authors: Jøntvedt Jørgensen M,Jenum S,Tonby K,Mortensen R,Walzl G,Du Plessis N,Dyrhol-Riise AM

    更新日期:2020-11-06 00:00:00

  • A simple and rapid method for isolation of eosinophilic granulocytes from human blood.

    abstract::A simple and rapid method for the purification of morphologically and functionally intact eosinophils from human blood of both normal and eosinophilic subjects is described. The method is based on a single centrifugation of total blood leukocytes suspended in Percoll with specific gravity 1.0853 g/ml, after erythrocyt...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.52.3.331

    authors: Cramer R,Dri P,Zabucchi G,Patriarca P

    更新日期:1992-09-01 00:00:00

  • The mouse interleukin (Il)33 gene is expressed in a cell type- and stimulus-dependent manner from two alternative promoters.

    abstract::GenBank entries for mouse Il33 reveal the existence of two transcripts, Il33a and Il33b, with different 5'UTRs but coding for the same protein. We investigated expression of these transcripts in different mouse organs and cell types in basal and inflammatory conditions. Il33a and Il33b mRNAs start with different nonco...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0811425

    authors: Talabot-Ayer D,Calo N,Vigne S,Lamacchia C,Gabay C,Palmer G

    更新日期:2012-01-01 00:00:00

  • Adhesion to extracellular matrix proteins modulates bovine neutrophil responses to inflammatory mediators.

    abstract::The neutrophil inflammatory response can be altered profoundly by contact with extracellular matrix proteins (ECMs). We characterized functional responses (intracellular calcium, actin polymerization, degranulation, adhesion, and oxidative burst) of bovine neutrophils adhered to selected ECM proteins [collagen IV, lam...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Borgquist JD,Quinn MT,Swain SD

    更新日期:2002-05-01 00:00:00

  • Frontline Science: Nasal epithelial GM-CSF contributes to TLR5-mediated modulation of airway dendritic cells and subsequent IgA response.

    abstract::Flagellin, as a TLR5 agonist, is an established mucosal adjuvant for enhancing mucosal IgA responses by i.n. immunization. Nasal epithelial cells (NECs) are the first sentinel cells to be exposed to antigen and adjuvant in i.n. immunization, and it is suggested that they play an important role in the mucosal adjuvant ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.3HI0816-368RR

    authors: Cao Y,Zhang E,Yang J,Yang Y,Yu J,Xiao Y,Li W,Zhou D,Li Y,Zhao B,Yan H,Lu M,Zhong M,Yan H

    更新日期:2017-09-01 00:00:00

  • Monitoring of neutrophil priming in whole blood by antibodies isolated from a synthetic phage antibody library.

    abstract::Neutrophil activation is a multistep process. In vitro activation of neutrophils with semiphysiological activators is optimal only after preactivation or priming with cytokines, chemotaxins, and/or bacterial products. Until now, no antibodies have been developed that can distinguish between resting and (cytokine) prim...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Koenderman L,Kanters D,Maesen B,Raaijmakers J,Lammers JW,de Kruif J,Logtenberg T

    更新日期:2000-07-01 00:00:00

  • Toll-like receptor 2 mediates inflammatory cytokine induction but not sensitization for liver injury by Propioni- bacterium acnes.

    abstract::Recognition of Gram-positive bacteria by Toll-like receptor 2 (TLR2) induces activation of proinflammatory pathways. In mice, sensitization with the Gram-positive Propionibacterium acnes followed by a challenge with the TLR4 ligand, lipopolysaccharide (LPS), results in fulminant hepatic failure. Here, we investigated ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0804448

    authors: Romics L Jr,Dolganiuc A,Velayudham A,Kodys K,Mandrekar P,Golenbock D,Kurt-Jones E,Szabo G

    更新日期:2005-12-01 00:00:00

  • Isolation and confinement as a model for spaceflight immune changes.

    abstract::The immune system of astronauts is disturbed during and after spaceflight. This situation may result from stressors encountered during the flight (microgravity, radiation, psychological stress, or confinement) or from physiological changes (demineralization or fluid shift). Therefore, ground-based investigations shoul...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/jlb.54.3.209

    authors: Schmitt DA,Schaffar L

    更新日期:1993-09-01 00:00:00

  • Factors mediating lipopolysaccharide-induced ganglioside expression in murine peritoneal macrophages.

    abstract::The ganglioside composition of endotoxin-responsive C3H/HeN murine peritoneal macrophages is known to undergo dramatic changes in vivo in response to intraperitoneal lipopolysaccharides (LPS), unlike endotoxin-hyporesponsive C3H/HeJ macrophages. To better investigate the mechanism behind LPS-induced macrophage ganglio...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.45.3.221

    authors: Berenson CS,Yohe HC,Ryan JL

    更新日期:1989-03-01 00:00:00

  • Concurrent evolution and resolution in an acute inflammatory model of rat carrageenin-induced pleurisy.

    abstract::Granulocyte apoptosis and subsequent clearance by phagocytes are critical for the resolution of inflammation. However, no studies have addressed how the resolution proceeds in the inflammatory site. We studied the time course of neutrophil apoptosis and the following ingestion by mononuclear leukocytes in rat carragee...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1002502

    authors: Murai N,Nagai K,Fujisawa H,Hatanaka K,Kawamura M,Harada Y

    更新日期:2003-04-01 00:00:00

  • Characterization of cytosolic proliferating cell nuclear antigen (PCNA) in neutrophils: antiapoptotic role of the monomer.

    abstract::We have shown previously that PCNA, a nuclear factor involved in DNA replication and repair in proliferating cells, is localized exclusively in the cytoplasm of neutrophils, where it regulates their survival. Nuclear PCNA functions are tightly linked to its ring-shaped structure, which allows PCNA to bind to numerous ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1212637

    authors: De Chiara A,Pederzoli-Ribeil M,Mocek J,Candalh C,Mayeux P,Millet A,Witko-Sarsat V

    更新日期:2013-10-01 00:00:00

  • Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis.

    abstract::Extravasation of leukocytes is a crucial process in the immunological defense. In response to a local concentration of chemokines, circulating leukocytes adhere to and migrate across the vascular endothelium toward the inflamed tissue. The small guanosinetriphosphatase Rap1 plays an important role in the regulation of...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0506357

    authors: Lorenowicz MJ,van Gils J,de Boer M,Hordijk PL,Fernandez-Borja M

    更新日期:2006-12-01 00:00:00