Abstract:
:Activation of beta2 integrins is necessary for neutrophil adhesion and full activation of neutrophil effector functions. We demonstrated previously that inhibition of protein kinase A (PKA) activity in quiescent neutrophils is sufficient to increase beta2-integrin cell surface expression, affinity, and adhesion. Thus, a tonic level of PKA activity prevents inappropriate activation of beta2 integrins in unstimulated neutrophils. Myosin light-chain (MLC) phosphorylation is an important regulator of leukocyte integrin function and adhesion. Moreover, PKA regulates MLC phosphorylation via inhibiting MLC kinase (MLCK) and MLC dephosphorylation via effects on the Rho kinase (ROCK)/MLC phosphatase pathway. We hypothesize that the tonic inhibitory effect of PKA on beta2-integrin activation neutrophils operates via its inhibition of MLC phosphorylation. We demonstrate here that inhibition of PKA activity with KT5720 activated beta2 integrins and adhesion coincident with an increase in MLC serine 19 (Ser 19) phosphorylation. KT5720-induced activation of beta2 integrins, adhesion, and MLC Ser 19 phosphorylation was abolished by pretreatment with the MLCK inhibitor ML-7 and specific MLCK inhibitory peptides but not the ROCK inhibitor Y-27632. These findings demonstrate that tonic PKA activity prevents activation of beta2 integrins and adhesion by inhibiting MLC phosphorylation via a MLCK-dependent but ROCK-independent pathway.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Chilcoat CD,Sharief Y,Jones SLdoi
10.1189/jlb.0405192subject
Has Abstractpub_date
2008-04-01 00:00:00pages
964-71issue
4eissn
0741-5400issn
1938-3673pii
jlb.0405192journal_volume
83pub_type
杂志文章abstract::Macrophages and dendritic cells are in the front line of host defense. When they sense host invasion, they produce cytokines that alert other innate immune cells and also abet the development of an adaptive immune response. Although lipolysaccharide (LPS), peptidoglycan, unmethylated DNA, and other microbial products ...
journal_title:Journal of leukocyte biology
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abstract::It has been shown recently that MCs are required for differential regulation of the immune response by granulocytic versus monocytic MDSCs. Granulocytic MDSCs promoted parasite clearance, whereas monocytic MDSCs enhanced tumor progression; both activities were abrogated in MC-deficient mice. Herein, we demonstrate tha...
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更新日期:2010-12-01 00:00:00
abstract::Human immunodeficiency virus (HIV) infection is characterized by viral entry into the central nervous system (CNS), which is mediated, in part, by the transmigration of HIV-infected monocytes into the brain. The elaboration of chemokines and other factors by these infected cells contributes to CNS inflammation and cog...
journal_title:Journal of leukocyte biology
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abstract::Alum, aluminum-hydroxide-containing compounds, long used as adjuvants in human vaccinations, functions by ill-defined, immunostimulatory mechanisms. Antigen-free alum has been shown to act via a previously unidentified, splenic Gr1(+), IL-4-expressing myeloid cell population to stimulate early B cell priming. We demon...
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doi:10.1189/jlb.0106005
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更新日期:2018-04-01 00:00:00
abstract::Initial studies designed to measure the effect of inhibiting RNA synthesis by dactinomycin on macrophage functions revealed that the cells were uniformly killed at concentrations that have been routinely used to inhibit RNA synthesis in other cell types. We, thus, determined the dose curve for the cytotoxicity of dact...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.57.4.635
更新日期:1995-04-01 00:00:00
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journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-11-01 00:00:00
abstract::Granulocyte-colony stimulating factor (G-CSF) is an essential cytokine, which contributes to proliferation and differentiation of granulocyte precursor cells in the bone marrow. Despite recent progress in understanding G-CSF signaling events, the mechanisms that underlie the distinct spectrum of biological functions a...
journal_title:Journal of leukocyte biology
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doi:10.1189/jlb.0205066
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abstract::Dendritic cells (DCs) loaded extracorporeally with antigen can be used as an adjuvant in vivo. In this work, we analyzed the migration of transferred DC and monitored the phenotype of new migrants in the draining lymph nodes. It is surprising that we found that a majority of resident DCs expressed donor MHC molecules ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
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更新日期:2007-10-01 00:00:00
abstract::HL-60 cells are promyelocytic leukemia cells that respond to culture conditions with differentiation into granulocytelike or macrophagelike phagocytes. O2 metabolism is critical to the microbicidal function of phagocytic cells. O2 metabolism was studied in HL-60 cells differentiated with dimethylsulfoxide (Me2SO) and ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.43.2.140
更新日期:1988-02-01 00:00:00
abstract::Exposure of the macrophage-like cell line J774.1 to 20 gray of cobalt-60 gamma radiation resulted in a block of tritiated thymidine incorporation, along with an increase in cell "activation," as assessed by increases in lysosomal enzyme and ectoenzyme content, PMA-induced H2O2 production, and NBT staining, ingestion o...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.38.3.369
更新日期:1985-09-01 00:00:00
abstract::C1qR(P) is a type I cell surface glycoprotein that has been shown to enhance ingestion of suboptimally opsonized targets by phagocytes in vitro. In this study, we developed and characterized polyclonal antibodies to study the tissue distribution of this receptor targeted to either the N- or C-terminal portion of the m...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
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journal_title:Journal of leukocyte biology
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doi:10.1189/jlb.5A0414-233RR
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abstract::The activation of dendritic cells (DC) via Toll-like receptors (TLRs) plays a decisive role in shaping the outcome of primary immune responses. Following TLR engagement by microbial products, DC migrate from peripheral tissues to lymphoid organs and up-regulate major histocompatibility complex and costimulatory molecu...
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doi:10.1189/jlb.0705392
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journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0803367
更新日期:2004-05-01 00:00:00
abstract::The recognition that apoptosis is regulated by an evolutionarily conserved set of polypeptides from the nematode Caenorhabditis elegans to humans suggests that a conserved set of biochemical mechanisms may also he involved in the response. Work from a number of independent laboratories suggests that alterations in cyt...
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更新日期:1996-06-01 00:00:00
abstract::Thimerosal is an organic mercury compound that is used as a preservative in vaccines and pharmaceutical products. Recent studies have shown a TH2-skewing effect of mercury, although the underlying mechanisms have not been identified. In this study, we investigated whether thimerosal can exercise a TH2-promoting effect...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
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abstract::The in vitro effects of 17 alpha AED, the isomer of 5-androstene-3 beta,17 beta diol (17 beta AED) on the basal growth of murine RAW 264.7, P388D1, and human HL-60 cells were investigated. 17 alpha AED treatment of RAW cells for 48 h reduced total cell number without increasing cell death as detected by trypan blue ex...
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abstract::The lineage-specific Charcot-Leyden crystal (CLC) protein is found in human eosinophils and basophils where it comprises 7-10% of the cellular protein content. Previous work from our laboratory has identified the motif GGAGA[A/G] as a powerful enhancer of gene transcription ill two eosinophil ribonuclease genes. To ev...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.67.5.691
更新日期:2000-05-01 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...
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journal_title:Journal of leukocyte biology
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journal_title:Journal of leukocyte biology
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更新日期:2000-06-01 00:00:00
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更新日期:1986-01-01 00:00:00