Abstract:
:We and others have established an important role for phosphoinositide-3 kinase gamma (PI3Kgamma) in the chemotactic responses of macrophages and neutrophils. The involvement of this lipid kinase in allergic inflammatory responses is, however, yet to be fully determined. Here we compare wild-type (WT) and PI3Kgamma(-/-) (KO) mice within a model of ovalbumin (OVA) -specific pulmonary inflammation. Upon OVA aerosol challenge, cell influx into the bronchoalveolar lavage (BAL) fluid consisted of neutrophils, macrophages and, more significantly, eosinophils - which are key effector cells in allergic inflammation. Each population was reduced by up to 80% in KO mice, demonstrating a role for PI3Kgamma in cell infiltration into the airways. The mechanism of reduced eosinophilia was analysed within both development and effector stages of the immune response. Comparable levels of OVA-specific T-cell proliferation and immunoglobulin production were established in both strains. Furthermore, no significant differences between WT and KO chemokine production were observed. Having identified the critical point of PI3Kgamma involvement, KO eosinophil chemotactic dysfunction was confirmed in vitro. These data are the first to demonstrate the vital role of PI3Kgamma in acute allergic inflammation. The profound dependency of eosinophils on PI3Kgamma for pulmonary influx identifies this lipid kinase as an attractive target for the pharmacological intervention of asthma.
journal_name
Immunologyjournal_title
Immunologyauthors
Thomas M,Edwards MJ,Sawicka E,Duggan N,Hirsch E,Wymann MP,Owen C,Trifilieff A,Walker C,Westwick J,Finan Pdoi
10.1111/j.1365-2567.2008.02908.xsubject
Has Abstractpub_date
2009-03-01 00:00:00pages
413-22issue
3eissn
0019-2805issn
1365-2567pii
IMM2908journal_volume
126pub_type
杂志文章相关文献
IMMUNOLOGY文献大全abstract::The activation of macrophages by various stimuli leading to chemotactic migration and phagocytosis is known to be mediated by an increase in intracellular Ca2+ concentration ([Ca2+]i). We measured changes in [Ca2+]i using a Ca2+ imaging method in individual human macrophages differentiated from freshly prepared periph...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.1999.00858.x
更新日期:1999-10-01 00:00:00
abstract::T helper type 17 (Th17) cells and regulatory T (Treg) cells are two distinct T-cell subsets with opposite effects on immune functions. While Th17 cells are a key effector in the immune response and play critical roles in the development of autoimmunity and inflammation, Treg cells orchestrate the overall immune respon...
journal_title:Immunology
pub_type: 杂志文章,评审
doi:10.1111/imm.12994
更新日期:2018-12-01 00:00:00
abstract::Although it is well known that cases with silicosis exhibit various immunological abnormalities, the mechanisms involved in the occurrence of immuno-dysfunction or dysregulation induced by silica compounds have not yet been determined. Fas is a well-known cell surface molecule that is involved in the apoptosis pathway...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.1998.00509.x
更新日期:1998-06-01 00:00:00
abstract::The localization of Thy-1, MRC OX 2 and Ia antigens as defined by monoclonal antibodies MRC OX 7, MRC OX 2 and MRC OX 6 was determined by an indirect immunoperoxidase technique on cryostat sections of rat ovaries. Thy-1 antigen was present significantly in the theca interna of growing antral follicles. Developing corp...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::It has previously been demonstrated that a gene on chromosome 1 in or near Mls-1 controls, on the surface of B cells, the mobility and aggregability of major histocompatibility complex (MHC) class II molecules but not the mobility or aggregability of other B-cell molecules, such as immunoglobulin (Ig) and class I anti...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::Large numbers of cells can be recovered from pig intestine with phenotypes suggesting lamina propria rather than intraepithelial origin. Following activation with concanavalin A these cells produced a T-cell growth factor (TCGF) activity which was not inhibited in the presence of a monoclonal antibody recognizing pig ...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The vitamin D receptor (VDR) is a nuclear receptor expressed in a number of different cells of the immune system. This study was performed to determine the effect of VDR deficiency on immune function and inflammation of the gastrointestinal tract in a model of inflammatory bowel disease, namely interleukin-10 (IL-10) ...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2005.02290.x
更新日期:2006-03-01 00:00:00
abstract::The influence of antigens of the major histocompatibility complex (MHC) on the production of interferon (IFN) alpha or IFN gamma by human peripheral blood leucocytes (PBL) in vitro has been studied. Synthesis of IFN gamma by PBL stimulated with purified phytohaemagglutinin (PHA-P) or protein A of Staphylococcus aureus...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1983-06-01 00:00:00
abstract::The effects of anti-Ia antibodies and cyclosporin A (CsA) on phenotypic differentiation of murine thymocytes were assessed in organ-cultured fetal thymuses. Both agents specifically abrogated the generation of CD4+8- thymocytes. Immunohistochemical studies revealed that Ia antigen on the organ-cultured thymic epitheli...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::Doxorubicin-stimulated whole rat glomeruli and dissociated mesangial and resident glomerular macrophage cells produced the release of interleukin (IL)-1 beta cytokine. This activity increased after the addition of lipopolysaccharide (LPS) or LPS plus indomethacin to the cultures. In the presence of WEB2086 [platelet-a...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::CXCL2 (macrophage inflammatory protein-2 (MIP-2)), a critical chemokine for neutrophils, has been shown to be produced in the rat intestine in response to platelet-activating factor (PAF) and to mediate intestinal inflammation and injury. The intestinal epithelium, constantly exposed to bacterial products, is the firs...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2006.02344.x
更新日期:2006-06-01 00:00:00
abstract::Endothelial cell activation antigens may play important roles in immune responses and in inflammation. This report describes the identification and characterization of a monoclonal antibody, named EAA-B, which reacts specifically with human umbilical vein endothelial (HUVE) cells pre-treated with tumour necrosis facto...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::Deficiency in gammadelta T cells aggravates colitis in animal models suggesting that gammadelta T cells have regulatory properties. Therefore, proliferation, suppression and cytokine secretion of human gammadelta T cells were determined in vitro. Human peripheral gammadelta T cells were isolated from the whole blood o...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2009.03162.x
更新日期:2009-12-01 00:00:00
abstract::Simultaneous kinetic measurements have been made of basophil degranulation and of histamine release. Both antigen and ionophore A23187 were studied. Cells from the same donor under the same conditions undergo both reactions at a similar rate. Regression analysis indicated a statistically highly significant correlation...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
abstract::Natural infection by mouse hepatitis virus (MHV) can affect interpretation of immunological studies in mice. MHV, a collective term describing a group of corona viruses, is found in natural infections in over 70% of laboratory mouse populations in the U.S.A. and Canada. Natural outbreaks of MHV in our animal colony af...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::The ultimate outcome of T cell receptor recognition is determined by the context in which the antigen is encountered. In this fashion both antigen-presenting cells and T cells must integrate multiple environmental cues in the form of pathogen-associated molecular patterns, cytokines and accessory molecule signals. The...
journal_title:Immunology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2567.2009.03125.x
更新日期:2009-08-01 00:00:00
abstract::The interaction between living groups A, C and G streptococci and IgG Fc was studied using human IgG, IgG Fc and IgG Fc-intermediate (Fci) fragments, chemically modified human IgG and fragment D of staphylococcal protein A (SPA). Diethylpyrocarbonate modification of His or N-acetylimidazole modification of Tyr of huma...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Two phenotypically distinct subpopulations of dendritic cells (SIRPalpha+ CC81Ag- DC and SIRPalpha- CC81Ag+ DC) have previously been identified in bovine afferent lymph which show functional differences when assayed in vitro. The purpose of this study was to investigate whether differences in cytokine production betwe...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.2003.01712.x
更新日期:2003-09-01 00:00:00
abstract::Cellular adhesion molecules play a central role in leucocyte migration through peripheral blood and tissues. A crucial stage in these events in selectin-mediated adhesion involving E-selectin expressed on activated endothelium interacting with a range of carbohydrate ligands expressed by specific subpopulations of leu...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::We studied proliferative responses of bovine T lymphocytes to foot-and-mouth disease virus (FMDV) serotypes A, O and C as well as to three peptides including the two major B-cell epitopes of FMDV (VP1[141-156] and VP1[200-213]). Peripheral blood mononuclear cells (PBMC) from cattle previously vaccinated with monovalen...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::We have previously shown that chlorpromazine (CPZ) inhibits tumour necrosis factor (TNF) production and protects against endotoxic shock in mice. In this paper we investigated the effect of pretreatment with CPZ, 4 mg/kg i.p. 30 min before, compared with dexamethasone (DEX; 3 mg/kg) on the induction of other endotoxin...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::Recently it has been shown that selective subconjunctival macrophage depletion reduced the incidence and severity of stromal herpes simplex virus (HSV) keratitis in mice. In this study, we examined the effect of conjunctival macrophage depletion on the corneal and systemic T-cell-mediated immune response. BALB/c mice ...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.2002.01477.x
更新日期:2002-09-01 00:00:00
abstract::Veiled cells (VC), isolated from the thoracic duct of irradiated lymphadenectomized mice (MLNX) or peritoneal macrophages (PM phi were incubated with isotope-labelled hen egg lysozyme (HEL), purified protein derivative (PPD) or keyhole limpet haemocyanin (KLH) in vitro. About 2-10 times less antigen was associated wit...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::It has been reported that, in early pregnancy in mice, there is an increase in the number of immunoglobulin-secreting cells in the lymph nodes which drain the uterus. This paper describes the results of further investigations provoked by interest in these early changes. Increases in the numbers of immunoglobulin-secre...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1985-06-01 00:00:00
abstract::Programmed death-1 (PD-1) plays an important role in protecting against inflammation and myocyte damage in T-cell-mediated myocarditis. To understand whether fibrinogen-like protein-2 (FGL2) can affect the role of the PD-1/PD-L1 pathway in experimental autoimmune myocarditis (EAM), we investigated cardiac function in ...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/imm.12837
更新日期:2018-02-01 00:00:00
abstract::Cancer immune surveillance is considered to be an important host protection process to inhibit carcinogenesis and to maintain cellular homeostasis. In the interaction of host and tumour cells, three essential phases have been proposed: elimination, equilibrium and escape, which are designated the 'three E's'. Several ...
journal_title:Immunology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2567.2007.02587.x
更新日期:2007-05-01 00:00:00
abstract::Studies of tuberculosis have suggested a shift in dominance from a T helper type 1 (Th1) towards a Th2 immune response that is associated with suppressed cell-mediated immune (CMI) responses and increased humoral responses as the disease progresses. In this study a natural host disease model was used to investigate th...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2004.02003.x
更新日期:2005-01-01 00:00:00
abstract::The immunomodulatory molecule cyclosporine was found to cause an early acceleration of the capping of mouse B-cell membrane immunoglobulin. This was most marked when the capping process was slightly retarded by keeping the cells at 32 degrees. This is a sign that the drug can cause B-cell membrane alterations. At lowe...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1986-04-01 00:00:00
abstract::An experiments in mice with a range of human serum albumin (HSA) molecules acylated to various degrees with side-chains of 6--20 carbon atoms, the greatest antibody responses against HSA were induced by highly acylated HSA with side-chains of intermediate length (C10--14). Similar results were obtained in rats but in ...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1980-03-01 00:00:00
abstract::Vitamins A and E and select flavonoids in the family of catechins are well-defined small molecules that, if proven to possess immunomodulatory properties, hold promise as vaccine adjuvants and various therapies. In an effort to determine the in vivo immunomodulatory properties of these molecules, we found that althoug...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/imm.12614
更新日期:2016-08-01 00:00:00