Abstract:
:Neutrophils are important mediators of the innate immune defense and of the host response to a physical trauma. Because aberrant infiltration of injured sites by neutrophils was shown to cause adverse effects after trauma, we investigated how neutrophil infiltration could be modulated at the cellular level. Our data indicate that protein kinase D (PKD) is a vital regulator of neutrophil transmigration. PKD phosphorylates the Cofilin-phosphatase Slingshot-2L (SSH-2L). SSH-2L in turn dynamically regulates Cofilin activity and actin polymerization in response to a chemotactic stimulus for neutrophils, for example, fMLP. Here, we show that inhibition of PKD by two specific small molecule inhibitors results in broad, unrestricted activation of Cofilin and strongly increases the F-actin content of neutrophils even under basal conditions. This phenotype correlates with a significantly impaired neutrophil deformability as determined by optical stretcher analysis. Consequently, inhibition of PKD impaired chemotaxis as shown by reduced extravasation of neutrophils. Consequently, we demonstrate that transendothelial passage of both, neutrophil-like NB4 cells and primary PMNs recovered from a hemorrhagic shock trauma model was significantly reduced. Thus, inhibition of PKD may represent a promising modulator of the neutrophil response to trauma.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Wille C,Eiseler T,Langenberger ST,Richter J,Mizuno K,Radermacher P,Knippschild U,Huber-Lang M,Seufferlein T,Paschke Sdoi
10.1002/JLB.4A0617-251RRsubject
Has Abstractpub_date
2018-09-01 00:00:00pages
615-630issue
3eissn
0741-5400issn
1938-3673journal_volume
104pub_type
杂志文章abstract::Intravenous administration of lipopolysaccharide (LPS) to rats increased the production of nitric oxide (NO) metabolites (NOx) by blood polymorphonuclear neutrophils (PMN) in vitro. Both dexamethasone and L-NMMA, added in vitro to neutrophil cultures, inhibited the production of NO. On the other hand, the production o...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.65.4.508
更新日期:1999-04-01 00:00:00
abstract::Inbred mouse strains have been known for many years to vary in their degree of susceptibility to different types of infectious diseases. The genetic basis of these interstrain differences is sometimes simple but often complex. In a few cases, positional cloning has been used successfully to identify single gene effect...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.1004616
更新日期:2005-06-01 00:00:00
abstract::The basal presence of immunologically potent cells within the intestinal muscularis externa and their functional significance is unclear. Our aim was to investigate the basal distribution of various leukocyte populations within the rat jejunal muscularis. In addition, we sought to immunohistochemically phenotype the m...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.63.6.683
更新日期:1998-06-01 00:00:00
abstract::Fluid-phase endocytosis is stimulated by H-ras-linked growth factor receptors and this stimulation requires activation of rab5. We utilized a GFP-rab5a:wt fusion protein to monitor GFP-rab5a:wt activation in living fibroblasts and in J774 macrophages. Control CHO cells that expressed GFP-rab5a:wt were cultured in seru...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::Immune exhaustion in T cells significantly impacts their ability to control malignancies and infections, and its discovery has led to revolutionary therapies for cancer in the form of checkpoint blockade. NK cells, like T cells, are lymphocytes that recognize virally infected and malignantly transformed cells. However...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/JLB.4MR0620-091R
更新日期:2020-10-01 00:00:00
abstract::Experimental autoimmune uveoretinitis (EAU) is a T helper type 1 cell-mediated autoimmune disease, which serves as a model of human chronic uveitis. In this model, cells of a monocyte/macrophage lineage and retinal antigen (Ag)-specific T cells infiltrate into the retina and cause inflammatory lesion, where proinflamm...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0805453
更新日期:2006-06-01 00:00:00
abstract::Nitric oxide (NO(.-)) contributes to vascular collapse in septic shock and regulates inflammation. Here, we demonstrate in lipopolysaccharide (LPS)-stimulated human THP-1 cells and monocytes that NO(.-) regulates interleukin (IL)-8 and tumor necrosis factor alpha (TNF-alpha) by distinct mechanisms. Dibutyryl-cyclic gu...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1203653
更新日期:2004-07-01 00:00:00
abstract::In this study we present data on a novel cell surface antigen recognized by monoclonal antibody (mAb) VPM30, originally thought to recognize only bovine and ovine sIg+ B cells from peripheral blood. Here we show that the antigen, molecular mass 28 kDa, is not only found in B cell follicles in frozen sections, but when...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.63.5.567
更新日期:1998-05-01 00:00:00
abstract::Postnatal stem cells regulate the homeostasis of the majority of our tissues. They continuously generate new progenitors and mature, functional cells to replace old cells, which cannot assume the tissue function anymore and are eliminated. Blood, skin, gut mucosa, muscle, cartilage, nerves, cornea, retina, liver, and ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0505272
更新日期:2005-10-01 00:00:00
abstract::Over 1.4 million Americans have been diagnosed with inflammatory bowel disease (IBD), and ulcerative colitis (UC) makes up approximately half of those diagnoses. As a disease, UC cycles between periods of remission and flare, which is characterized by intense abdominal pain, increased weight loss, intestinal inflammat...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.4MA1217-506R
更新日期:2018-09-01 00:00:00
abstract::CD163, a monocyte and macrophage-specific surface glycoprotein, which is increased by interleukin-10 and glucocorticoids, is a scavenger receptor for hemoglobin/haptoglobin complexes. We report a rapid and highly reproducible rise in soluble CD163 in the plasma of human volunteers given intravenous lipopolysaccharide ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract::Binding of a potent chemotactic formyl tetrapeptide, formylmethionyl-leucyl-phenylalanyl-phenylalanine (fMet-Leu-Phe-Phe), to the formyl peptide receptors on the rabbit neutrophil was assessed by two approaches. A tritiated preparation of fMet-Leu-Phe-Phe was used for direct binding studies, whereas indirect studies c...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.43.5.420
更新日期:1988-05-01 00:00:00
abstract::In newborn infants, the innate cellular system plays a crucial role in the first line of defense against pathogens. Neutrophils are the most abundant leukocytes, and their response to the commonly encountered nosocomial bacterial (Gram positive) infection in newborns remains largely unclear. In this study, a genome-wi...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0413219
更新日期:2014-01-01 00:00:00
abstract::Diabetes is both a metabolic and an immune disorder. One intriguing link between the two is the serine-threonine protein kinase mammalian target of rapamycin (mTOR). As a component of the PI3K/Akt pathway and other cellular signals, mTOR is a key regulator of fuel metabolism and function of both pancreatic islet β cel...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/JLB.3MR0317-095RR
更新日期:2018-01-09 00:00:00
abstract::Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the leading global cause of death from an infectious agent. Mycobacteria thrive within their host Mϕs and presently, there is no animal model that permits combined in vitro and in vivo study of mycobacteria-host Mϕ interactions. Mycoba...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.1A0919-147R
更新日期:2019-12-01 00:00:00
abstract::The objective of this study was to find the role of LncRNA SNHG12 in the regulation of hypertensive vascular endothelial injury. LncRNA SNHG12 and miR-25-3p expression were detected by quantitative RT-PCR. Protein levels of Sirtuin 6 (SIRT6), endothelial cell (EC) senescence markers p16 and p21, and EC marker CD31 wer...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.1A0820-501R
更新日期:2021-01-19 00:00:00
abstract::A protein with interleukin 1 (IL-1) activity was obtained from the human acute monocytic leukemia cell line (THP-1) and purified by ultrafiltration, Ultrogel AcA54 chromatography, isoelectric focusing, and discontinuous polyacrylamide gel electrophoresis. Like the pI 6.8 species of IL-1 from human peripheral blood mon...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.37.5.511
更新日期:1985-05-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that plays a pivotal role in mediating neovascularization as well as other endothelial cell alterations during inflammation. In this study, we demonstrate that human neutrophils are a source of VEGF. We observed that isolated blood neutrophils rel...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.62.3.397
更新日期:1997-09-01 00:00:00
abstract::LPS has been widely used to induce inflammatory pain, attributing to production of inflammatory cytokines and sensitization of nociceptors. Paeoniflorin (PF) possesses anti-nociceptive property, but its effect on LPS-induced inflammatory pain has not been investigated. In this study, we aimed to investigate the analge...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.3MA0220-355R
更新日期:2020-07-01 00:00:00
abstract::Little is known about the roles of galectins, a family of beta-galactoside-binding lectins, in myeloid cell differentiation. In the present experiments, we used HL-60 cells as a model of myeloid cell differentiation. The HL-60 cells were differentiated into eosinophil-, monocyte-, and neutrophil-like cells by cocultur...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0402163
更新日期:2003-05-01 00:00:00
abstract::Mast cell activation requires Cl(-) flux, which maintains the driving force for entry of extracellular calcium and initiates release of mediators such as histamine. However, chloride channel expression in mast cells has been poorly understood. For the first time, reverse transcriptase-polymerase chain reaction shows t...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::CXC chemokines, which induce angiogenesis, have glutamine-leucine-arginine amino acid residues (ELR motif) in the amino terminus and bind CXCR2 and the Duffy antigen chemokine-binding protein. Duffy, a seven transmembrane protein that binds CXC and CC chemokines, has not been shown to couple to trimeric G proteins or ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::Changes in leukocyte subpopulations and function after spaceflight have been observed but the mechanisms underlying these changes are not well defined. This study investigated the effects of short-term spaceflight (8-15 days) on circulating leukocyte subsets, stress hormones, immunoglobulin levels, and neutrophil func...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.65.2.179
更新日期:1999-02-01 00:00:00
abstract::Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by the presence of multiple senile plaques in the brain tissue, which are also associated with considerable inflammatory infiltrates. Although the precise mechanisms of the pathogenesis of AD remain to be determined, the overproduction ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:
更新日期:2002-10-01 00:00:00
abstract::Human neutrophils isolated from the blood were incubated in vitro for 30 min with 25 ng/ml of phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, to study its effect on the fine structure of granulocytes and on the subcellular distribution of lactoferrin (Lf). Flow cytometry analysis of the human neut...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.50.5.444
更新日期:1991-11-01 00:00:00
abstract::IL-27, an IL-12 family member, was initially described as a proinflammatory cytokine. Nevertheless, it also poses anti-inflammatory activity, being involved in suppressing development of TH-17 cells as well as in the induction of inhibitory Tr1 cells. Recent data obtained in mice suggest that it can down-modulate the ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1209788
更新日期:2011-06-01 00:00:00
abstract::Rac2 is a hematopoietic-specific Rho-GTPase that plays a stimulus-specific role in regulating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and other functional responses in neutrophils. In this study, rac2-/- neutrophils were shown to have significantly decreased NADPH oxidase activit...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0705371
更新日期:2006-01-01 00:00:00
abstract::This study addresses the role of (pro)MMP-9 overexpression in CLL cell migration. We have used primary CLL cells and CLL-derived MEC-1 cells transfected with empty (mock cells) or proMMP-9-encoding (MMP-9 cells) lentiviral vectors. The constitutive (pro)MMP-9 expression in mock cells and primary CLL cells was similar,...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0913521
更新日期:2014-03-11 00:00:00
abstract::ANCA to either PR3 or MPO are found in patients with necrotizing vasculitis and glomerulonephritis. ANCA binding to their target antigens on neutrophils and subsequent neutrophil activation are pivotal disease mechanisms that lead to vascular inflammation and necrosis. ANCA interaction with PR3 is more complex than wi...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.5A0116-037R
更新日期:2016-12-01 00:00:00
abstract::High mobility group box 1 (HMGB1) is one of the recently defined damage-associated molecular pattern molecules, passively released from necrotic cells and secreted by activated macrophage/monocytes. Whether cytolytic cells induce HMGB1 release from tumor cells is not known. We developed a highly sensitive method for d...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0306169
更新日期:2007-01-01 00:00:00