Abstract:
:MMPs are generally considered to regulate degradation and remodeling of the ECM. Convincing data also implicate a role for MMPs in inflammatory conditions, such as AP, although the mechanisms are not known. The aim of this study was to define the role of MMPs in regulating activation of trypsinogen and tissue damage in AP, which was induced by infusion of taurocholate into the pancreatic duct in mice. A broad-spectrum MMP inhibitor (BB-94) and MMP-9 gene-deficient mice were used. Neutrophil secretions and rMMP-9 were used to stimulate trypsinogen activation in isolated acinar cells. Taurocholate challenge increased serum amylase, neutrophil infiltration, MIP-2 (CXCL2) formation, trypsinogen activation, and tissue damage in the pancreas. Treatment with the broad-spectrum inhibitor of MMPs, BB-94, markedly reduced activation of trypsinogen, levels of CXCL2, infiltration of neutrophils, and tissue damage in AP. Taurocholate challenge increased serum levels of MMP-9 but not MMP-2. Taurocholate-induced amylase levels, neutrophil accumulation, production of CXCL2, trypsinogen activation, and tissue damage in the pancreas were abolished in MMP-9-deficient mice. Moreover, secretions from activated neutrophils isolated from WT but not from MMP-9-deficient animals stimulated trypsinogen activation in acinar cells. Notably, rMMP-9 greatly enhanced activation of trypsinogen in acinar cells. These findings demonstrate that neutrophil-derived MMP-9 is a potent activator of trypsinogen in acinar cells and regulates pathological inflammation and tissue damage in AP.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Awla D,Abdulla A,Syk I,Jeppsson B,Regnér S,Thorlacius Hdoi
10.1189/jlb.0811443subject
Has Abstractpub_date
2012-05-01 00:00:00pages
711-9issue
5eissn
0741-5400issn
1938-3673pii
jlb.0811443journal_volume
91pub_type
杂志文章abstract::CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are substantially expressed in...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1005602
更新日期:2006-04-01 00:00:00
abstract::Human alveolar macrophages (AMO) have been investigated for their ability to produce three monokines, tumor necrosis factor-alpha (TNF), macrophage colony stimulating factor (CSF-1), and interleukin 1-beta (IL-1). No TNF activity was found in supernatants of unstimulated AMO cultured for 20 h, although TNF mRNA was de...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::Concanavalin A (Con A)-induced hepatitis is a model for human T cell-mediated hepatitis. We evaluated the role of L-selectin and intercellular adhesion molecule-1 (ICAM-1) in this model by injecting Con A intravenously in mice lacking L-selectin (L-selectin-/-), ICAM-1 (ICAM-1-/-), or both (L-selectin/ICAM-1-/-). Bloo...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0905527
更新日期:2006-04-01 00:00:00
abstract::Although tumor growth enhances macrophage (m phi) cytotoxic activity by increasing their tumor necrosis factor-alpha (TNF-alpha) production, increased prostaglandin E2 (PGE2) synthesis reduces most immune responses during tumor growth. Macrophages that do not express major histocompatibility complex class II molecules...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.53.5.550
更新日期:1993-05-01 00:00:00
abstract::LPS induces dendritic cell (DC) activation, but the precise in vivo mechanism is unclear since DCs express low levels of TLR4. Here, it is shown that DCs can be activated in response to LPS through a bystander mechanism. This result was obtained using chimeric mice reconstituted with LPS-responsive and nonresponsive b...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0406253
更新日期:2006-12-01 00:00:00
abstract::Therapeutic manipulation of cellular apoptosis holds great promise for malignant and potentially nonmalignant diseases. A relative resistance to apoptosis in RA synovium is associated with increased expression of prosurvival Bcl-2 family members. In this study, we demonstrate that treatment of DBA/1 mice, prior to the...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0311174
更新日期:2011-10-01 00:00:00
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:
更新日期:2000-07-01 00:00:00
abstract::Polymorphonuclear leukocytes (PMNs) exert most of their physiological functions while adherent to surfaces rather than in suspension. PMN adhesion is largely dependent on the function of the beta 2 integrins, CD11a,b,c/CD18. We mimicked engagement of beta 2 integrins by antibody cross-linking of CD18 on isolated human...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.56.5.625
更新日期:1994-11-01 00:00:00
abstract::The Charcot-Leyden crystal (CLC) protein, a prominent cell constituent unique to eosinophils and basophils, possesses lysophospholipase activity. This activity and the extracellular deposition and formation of CLC in tissues and body fluids in association with eosinophils suggest an extracellular function for this pro...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.51.4.386
更新日期:1992-04-01 00:00:00
abstract::Serum MBP, also known as MBL, is a C-type lectin that is known to be a soluble host defense factor involved in innate immunity. It has been well established that dying microbes and apoptotic cells release highly viscous DNA that induces inflammation and septic shock, and apoptotic cells display fragmented DNA on their...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1008674
更新日期:2009-09-01 00:00:00
abstract::Neutrophils are the most abundant leukocytes in blood. From the circulation, they are quickly mobilized to sites of inflammation and/or infection. At the affected tissues, neutrophils display an impressive array of antimicrobial functions, including degranulation, production of reactive oxygen species (ROS), phagocyto...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/JLB.4MIR0220-574RR
更新日期:2020-07-01 00:00:00
abstract::STAT1 is a key effector of cytokines involved in the resistance to pathogens; its identified transcriptional targets mediate the innate immune response involved in the defense against viruses and bacteria. Little is known about the role of STAT1 in adaptive immunity, including its impact on BCR or surface Ig expressio...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1109714
更新日期:2010-06-01 00:00:00
abstract::The influence of ethanol (EtOH) on multiple dendritic cell (DC) subsets, in the steady state or following their mobilization in vivo, has not been characterized. Herein, generation of mouse bone marrow-derived DC (BMDC) in response to fms-like tyrosine kinase 3 ligand was inhibited by physiologically relevant concentr...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0905517
更新日期:2006-05-01 00:00:00
abstract::Autoreactive CD4+ and CD8+ T cells directed against CNS autoantigens may play a role in the development of multiple sclerosis (MS). Identical twins share the same genetic background but not the TCR repertoire that is shaped by the encounter with self or foreign antigens. To gain insights into the interplay between MS ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0906584
更新日期:2007-03-01 00:00:00
abstract::The kinetics and regulatory mechanisms of T cell migration through the endothelium have not been fully defined. In experimental, filter-based assays in vitro, transmigration of lymphocytes takes hours, compared with minutes, in vivo. We cultured endothelial cell (EC) monolayers on filters, solid substrates, or collage...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0508301
更新日期:2009-01-01 00:00:00
abstract::Hepatic Macs, consisting of resident KCs and infiltrating monocytes/IMs, are thought to play an important role in the pathogenesis of ALD. Previous work has focused on KCs or studied hepatic Macs as one cell population. The aim of the current study is to distinguish IMs from KCs and to compare their phenotypes and fun...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.6A0114-004RR
更新日期:2014-10-01 00:00:00
abstract::Many intracellular signals, such as host danger-associated molecules and bacterial toxins during infection, elicit inflammasome activation. However, the mechanical environment in tissues may also influence the sensitivity of various inflammasomes to activation. The cellular mechanical environment is determined by the ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/JLB.3MIR1118-417R
更新日期:2019-07-01 00:00:00
abstract::Maturation of cells of the mononuclear phagocyte lineage from bone marrow precursors to tissue macrophages (MAC) via circulating blood monocytes (MO) is a multistep process only partially understood. Similarly, MAC differentiation can be observed if MO are cultured in vitro. In an attempt to further characterize molec...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.60.4.540
更新日期:1996-10-01 00:00:00
abstract::Rats were injected with phenylhydrazine (PHZ) for periods of up to 6 months, during which time a marked leukocytosis was induced. The highest leukocyte counts occurred within 4-5 days following injection. An initial injection of 4 mg/100 gm body weight evoked a mean total leukocyte count of 129 X 10(3) cells/microlite...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.39.1.37
更新日期:1986-01-01 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::A previously unsuspected, considerable proportion of newly synthesized polypeptides are hydrolyzed rapidly by proteasomes, possibly competing with endogenous substrates and altering proteostasis. In view of the anti-cancer effects of PIs, we set out to achieve a quantitative assessment of proteasome workload in cells ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1011497
更新日期:2012-11-01 00:00:00
abstract::Extracellular ATP mediates a diverse array of biological responses in many cell types and tissues, including immune cells. We have demonstrated that ATP induces purinergic receptor P2X(7) mediated membrane permeabilization, apoptosis, and cytokine expression in murine mast cells (MCs). Here, we report that MCs deficie...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,收录出版
doi:10.1189/jlb.0808470
更新日期:2009-04-01 00:00:00
abstract::The macrophage mannose receptor (MR) appears to play an important role in the binding and phagocytosis of several human pathogens, but its phagocytic property and signaling pathways have been poorly defined. The general strategy to explore such topics is to express the protein of interest in nonphagocytic cells, but i...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1204705
更新日期:2005-06-01 00:00:00
abstract::Eosinophils were isolated from peritoneal lavages of repeated horse serum-injected guinea pigs or rhesus monkeys and from peripheral blood of normal human donors. Eicosanoid metabolism and chemotaxis by these cells were studied by in vitro techniques. Upon calcium ionophore stimulation guinea pig eosinophils released ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.50.2.140
更新日期:1991-08-01 00:00:00
abstract::We investigated the kinetics of macrophage subpopulations and the expression of monocyte chemoattractant protein 1 (MCP-1) in a rat model of bleomycin-induced lung injury. Rat macrophage subpopulations were examined by immunohistochemistry using various anti-rat macrophage monoclonal antibodies (mAbs) and their prolif...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.56.6.741
更新日期:1994-12-01 00:00:00
abstract::The role of JNK in neutrophil chemotaxis and killing of microbial pathogens remains unclear. Using a recently described cell-permeable peptide inhibitor of the JNK pathway, based on the JBD of JIP-1, coupled to the protein transduction domain of HIV-TAT (TAT-JIP), in association with control peptides, we demonstrate t...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0609399
更新日期:2010-05-01 00:00:00
abstract::The role of Myeloid-Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with infant vaccine responses throughout the first year of life in a prospective cohort study. Ninety-one South African infant-mother pairs were enrolled at delivery, and blood s...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.5A0420-281R
更新日期:2021-01-21 00:00:00
abstract::The specific binding of human polymorphonuclear leukocytes (PMN) to antibody-coated target cells was characterized by flow cytometry. PMN were labeled with phycoerythrin-E (PE) via a granulocyte-specific monoclonal antibody (leu-M1) and mixed with fluorescein isothiocyanate-labeled K562 tumor cells sensitized with rab...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.46.5.467
更新日期:1989-11-01 00:00:00
abstract::Multiple mechanisms are used by the human immunodeficiency virus type 1 (HIV-1) to interfere with host-cell immune effector functions. The 27-kD Nef protein has been shown to down-modulate specific genes of the major histocompatibility complex class I (MHC-I) on the surface of infected primary T cells, facilitating th...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0505237
更新日期:2005-09-01 00:00:00
abstract::CEACAM6 (CD66c) and CEACAM8 (CD66b) are cell-adhesion proteins on neutrophils that belong to the human carcinoembryonic antigen (CEA) family. CEACAM6 reveals homophilic adhesion and heterophilic adhesion to other CEACAM family antigens including CEACAM8, CEACAM1, and CEA, whereas CEACAM8 exhibits only heterophilic adh...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00