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At least 1,099 records · Page 61Linked to original sources
PubMed1992

Epidermal keratinocyte-derived basophil promoting activity. Role of interleukin 3 and soluble CD23.

Human epidermal keratinocytes (EK) secrete factors able to sustain the proliferation of early myeloid cells and, in particular, the generation of basophils. This activity was previously attributed to IL-3, although no definitive in situ demonstration of this cytokine was provided. In regard to the possible physiological relevance of these data, we investigated herein the nature of EK-derived factors responsible for basophil promotion. Our data show that EK-derived supernatants (EK-sup) contain IL-3 as well as soluble CD23 (sCD23), both known for their colony stimulating activity. Messenger RNA for IL-3 and CD23 were also detected in EK. Blocking experiments using specific neutralizing monoclonal antibodies (mAb) further indicate that EK-derived basophil promoting activity is mainly due to the presence of IL-3 and sCD23 in EK-sup. Furthermore, by contrast to IL-3, sCD23 secretion by EK is cortisone sensitive and highly enhanced by IL-4, suggesting distinct regulatory mechanisms for their production.

Antibodies, Monoclonal↗
PubMed2002

C5a stimulates production of plasminogen activator inhibitor-1 in human mast cells and basophils.

We have recently shown that resting human mast cells (MCs) produce tissue-type plasminogen activator (t-PA) without simultaneously expressing plasminogen activator inhibitor 1 (PAI-1). In the present study we have identified the anaphylatoxin rhC5a as a potent inducer of PAI-1 expression in human MCs and basophils. In primary human skin MCs and primary blood basophils, exposure to rhC5a was followed by an increase from undetectable to significant levels of PAI-1. In addition, rhC5a induced a concentration- and time-dependent increase in PAI-1 antigen in the MC line HMC-1 and the basophil cell line KU-812 and increased the expression of PAI-1 mRNA in HMC-1. In conditioned media of HMC-1 treated with rhC5a, active PAI-1 could be detected. A simultaneous loss of t-PA activity in conditioned media from the same cells indicated that rhC5a-induced PAI-1 was capable of inhibiting the enzymatic activity of coproduced t-PA. Correspondingly, the levels of t-PA-PAI-1 complexes increased in rhC5a-treated cells. When HMC-1 cells were incubated with pertussis toxin or anti-C5a receptor antibodies, the effect of rhC5a on PAI-1 production was completely abolished. Treatment of C5a with plasmin resulted in loss of its ability to induce PAI-1 production in MCs. Considering the suggested role for MCs and components of the complement system in the development of cardiovascular diseases, we hypothesize that MCs, by producing t-PA in a resting state and by expressing PAI-1 when activated by C5a, might participate in the modulation of the balance between proteases and protease inhibitors regulating tissue injury and repair in such disease processes.

Antigens, CD↗
PubMed1994

Pulmonary immune cells in health and disease: mast cells and basophils.

Mast cells and basophils are multifunctional immune cells and have been implicated in the pathogenesis of asthma and other pulmonary diseases. Although they are derived from distinct lineages, they share a number of important features which justifies discussing them collectively. This review covers the cellular characteristics and biological properties of both cell types, including origin, maturation and differentiation, morphological and phenotypical properties, as well as their capacity to secrete preformed and newly generated mediators of inflammation. In addition, the mechanisms of cell activation and priming of mast cells and basophils will be outlined, as well as the putative mechanisms through which both cell types communicate with other inflammatory cells. The final section of the review focuses on the possible pathogenetic role of mast cells and basophils in several pulmonary diseases, such as parasitic infections, allergic diseases, pulmonary fibrosis and malignant disorders.

Animals↗
PubMed2003

Basophils express a type 2 cytokine profile on exposure to proteases from helminths and house dust mites.

The proteolytic activities frequently associated with sources of allergens and parasite secretions have been suggested as important immunomodulators. We have investigated whether the protease activity of the house dust mite allergen Der p1 and the secreted proteases of the hookworm Necator americanus are able to directly induce type 2 cytokine production by basophils. Der p1 and the secretions of N. americanus induced interleukin (IL)-4, IL-5, and IL-13 but not interferon-gamma mRNA in KU812 basophils. Enzyme-linked immunosorbent assay confirmed that IL-4 and IL-13 were secreted. A nonproteolytic antigen failed to induce cytokine expression, and preincubation of Der p1 or N. americanus secretions with protease inhibitors inhibited cytokine expression. Data were confirmed using basophils purified from human peripheral blood. We speculate that this innate mechanism may contribute to the development of a cytokine milieu that could promote immunoglobulin E synthesis, eosinophil recruitment, and the development of type 2 T cells.

Animals↗
PubMed1976

Basophilic meningitis secondary to lymphoma.

In this case report of basophilic meningitis, the patient was a 5-year-old girl under treatment for a diffuse lymphocytic lymphoma. She presented with headache and bilateral papilledema. Cerebrospinal fluid examination showed 60 percent basophils. Subsequent specimens showed a rare blast. It is postulated that after the lymphoma cells had spread to the meninges, a cell-mediated immune reaction was initiated with the appearance of basophils in the exudate.

Basophils↗
PubMed1999

IPD-1151T (suplatast tosilate) inhibits interleukin (IL)-13 release but not IL-4 release from basophils.

The effect of suplatast tosilate (IPD-1151T), which is known to suppress interleukin (IL)-4 release from T cells, on the release of IL-4 and IL-13 from human peripheral basophils was investigated. Basophils were obtained from 16 mite-sensitive atopic asthmatic patients. IPD-1151T clearly inhibited the antigen-induced release of IL-13 but not IL-4. These results suggest that IPD-1151T possesses different activity for the regulation of cytokine release in basophils and T cells.

Adult↗
PubMed1997

Regulation of the function of eosinophils and basophils.

Both eosinophils and basophils play active pathogenic roles in the inflammation associated with allergic disorders. Both types of cells share a majority of their cell surface structures, and because of these common surface molecules, both cells can be stimulated with a single ligand simultaneously. The growth of both types of cells is controlled by IL-3, GM-CSF, and IL-5. All three growth factors are also capable of priming both eosinophils and basophils for enhanced biological functions, such as increased mediator release and prolonged survival. Both cells express beta 2 integrins, and in contrast to neutrophils, they also express several beta 1 integrins. Ligation of these adhesion molecules also transduces the intracellular signal leading to regulation of the cellular functions. In this review, we briefly describe the effects of various ligands of surface receptors and several pharmacological compounds on the functions of human eosinophils and basophils.

Animals↗
PubMed2006

Roles of IL-18 in basophils and mast cells.

Basophils and mast cells are effecter cells in allergen/IgE-mediated immune responses. They induce type 1 immediate immune response in airway or other organ, resulting in bronchial asthma and other allergic diseases. However, they also play a critical role in host defense against infection with helminthes. Upon linkage of FcepsilonRI with a complex of allergen and IgE, basophils and mast cells release a large amount of Th2 cytokines and chemical mediators. Therefore these responses are "acquired allergic responses" and induce allergic diseases, such as bronchial asthma. However, basophils and mast cells derived from cultured bone marrow cells with IL-3 for 10 days express IL-18Ralpha chain and produce Th2 cytokines in response to the stimulation with IL-3 and IL-18 without FcepsilonRI cross-linkage. Furthermore, they produce Th2 cytokines upon stimulation with several TLR ligands, such as LPS. This finding may suggest the presence of allergen/IgE-independent allergic responses, which we would like to designate as "innate allergic response". However, in vivo treatment with IL-18 and IL-2 protects against gastrointestinal nematode infection by activating intestinal mucosal mast cells in STAT6-independent manner, suggesting the importance of innate allergic response against helminth infection. Here we discuss the functional role of IL-18-induced "innate allergic response" in disease and host defense.

Animals↗
PubMed1998

IgE-mediated desensitization in human basophils and mast cells.

Secretion from mast cells and basophils, two cells central to immediate hypersensitivity reactions, has characteristics that suggest the existence of intrinsic signal transduction processes that limit the extent of the cell's response. This process(es) has been termed desensitization. One goal of current research efforts is to determine the mechanisms used by mast cells and basophils to down-regulate an ongoing secretory reaction. Recent studies have indicated that, like secretion itself, the mechanisms of down-regulation or desensitization differ according to the mediator being studied. Thus, for human basophils, there appear to be distinct signaling pathways leading to the secretion of the three major classes of mediators--granules contents, lipids, and cytokines--and each pathway appears to have distinct down-regulatory processes. For an ongoing secretory reaction, the secretion of histamine and LTC4 are limited by a process that does not involve the earliest steps in activation, activation of the early tyrosine kinases, lyn and syk. These early events persist for long periods which more appropriately correspond to the regulation of cytokine secretion. Recent studies have also indicated that the process of desensitization is altered during stimulation in the absence of extracellular calcium, the traditional method of examining this process. These studies indicate that down-regulation studied in this manner is not dependent on any of the signaling events currently defined as being necessary for secretion. A variety of processes are discussed and potential mechanisms based on most recent studies using cell lines are explored.

Animals↗
PubMedDate not supplied

Cutaneous basophil hypersensitivity in the guinea pig conjunctiva.

Cutaneous basophil hypersensitivity (CBH) is an immunologic reaction extensively studied in the guinea pig. We elicited this reaction in the conjunctiva by systemically sensitizing guinea pigs to ovalbumin in incomplete Freund's adjuvant. Skin tests showed basophils in the skin one week after sensitization when challenged with ovalbumin. However, the conjunctiva showed an eosinophilic reaction with few basophils. This is compatible with other extracutaneous manifestation of the CBH reaction.

Animals↗
PubMed1995

A beta 2-agonist, procaterol, inhibits basophil migration.

Beta 2-receptor agonists have recently been reported to be effective on allergen-induced late-phase reaction (LPR) in addition to their inhibitory effect on immediate-phase reaction, although the precise mechanism is not fully understood. In this study, we tested the effect of a selective beta 2-agonist, procaterol, on human basophil migration, which may be an important characteristic of LPR. Procaterol inhibited IL-8- and C5a-induced basophil migration in a dose-dependent fashion; 10(-7) M of procaterol reduced 30% of migration induced by both factors. The action of procaterol was rapid since the inhibition of migration was detected without preincubation and was not via the toxic effect on basophils as assessed by trypan blue test. The results of this study extend the repertoire of anti-inflammatory actions of beta 2-agonists.

Adrenergic beta-Agonists↗
PubMed1992

Autoimmune vasculitis in MRL/Mp-lpr/lpr mice: orthochromatic basophils participate in the development of delayed-type hypersensitivity angiitis.

The pathogenesis of autoimmune vasculitis is poorly understood. Understanding the immunologic mechanisms governing this disease requires precise identification of the cells which comprise the lesion. In this report, we have evaluated tissue sections from MRL/lpr mice from 16 to 45 weeks of age, representing all stages of clinical vasculitis. We demonstrate that basophil myelocytes participate in the evolution of the delayed-type hypersensitivity (DTH) response which initiates and perpetuates autoimmune vasculitis in these mice. These findings raise questions regarding the immunologic mechanisms by which basophils develop in this lesion and the interaction of basophils. VSMCs and lymphocytes in vasculitic angiodestruction.

Animals↗
PubMed1996

Mast cell-lineage versus basophil lineage involvement in myeloproliferative and myelodysplastic syndromes: diagnostic role of cell-immunophenotyping.

Mast cells and blood basophils are distinct hemopoietic cells. They can be distinguished from each other and from all other lymphohemopoietic cells using antibodies against surface receptors or stored cytoplasmic molecules. In patients with myelodysplastic syndromes (MDS) or myeloproliferative syndromes (MPS), an elevation of metachromatically granulated cells (MCS) is frequently seen. These cells can be classified as basophils or mast cells using monoclonal antibodies (mAbs) against leukocyte antigens, including mast cell tryptase, c-kit (= mast cell growth factor [MGF] receptor), interleukin-3 receptor alpha chain (IL-3R alpha = CD123), and CD11b (C3biR). In a stable phase of MDS or MPS, the circulating MCS usually are basophils (histamine+, tryptase-, c-kit-, IL-3R alpha +, CD11b+). In an accelerated or terminal phase of disease, however, mast cell lineage involvement and circulating mast cell precursors (histamine+, tryptase+, c-kit+, IL-3R alpha-, CD11b-) are found in a subset of patients. The use of mAbs against mast cell antigens and granulocyte antigens is diagnostic in these patients.

Basophils↗
PubMed2000

Requirements for C5a receptor-mediated IL-4 and IL-13 production and leukotriene C4 generation in human basophils.

Anaphylatoxin derived from the fifth complement component (C5a) in the presence of IL-3 induces continuous leukotriene C4 generation and IL-4 and IL-13 expression in human basophils for a period of 16-18 h. This indicates that the G protein-coupled C5a receptor (C5aR) can induce long-lasting cellular responses. Using anti-N-terminal C5aR Abs, C-terminal C5a hexapeptide analogs, and pertussis toxin, we demonstrate that the putative activation site of the C5aR is both necessary and sufficient for these late cellular responses. Furthermore, continuous pertussis toxin-sensitive G protein-coupled receptor activation and receptor-ligand interaction is ongoing and required during the entire period of product release. However, the late basophil responses have a more stringent requirement for optimal receptor activation. Leukotriene C4 generation appears to be influenced mostly by the way the receptor is activated, because the most active hexapeptide is a superagonist for this response. By contrast, C5adesarg, lacking the C-terminal arginine, induces minimal lipid mediator formation but is fully active to induce IL-4 production and is even a superagonist for IL-13 release. Nevertheless, IL-4/IL-13 synthesis in response to C5adesarg could be blocked by both C-terminal antagonistic peptide as well as anti-N-terminal C5aR Abs, indicating only minor differences of ligand-receptor interactions between C5a and C5adesarg. Taken together, our data demonstrate that long-lasting and continuous signaling occurs through a limited activation domain of the C5aR, which can differentially promote separate basophil functions.

Antigens, CD↗
PubMed2005

Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production.

Mast cells, basophils, and eosinophils are myeloid cells that are distinguished by their capability to produce IL-4 and IL-13. However, it is not clear how this potential is related to the lineage differentiation of these subsets. In the present study we used bicistronic IL-4 reporter (4get) mice to directly visualize IL-4 expression by nonlymphoid cells in vitro and in vivo at the single-cell level. Our data show that frequent expression of both Il4 alleles is initiated and maintained during ontogeny by an IL-4Ralpha- or Stat6-independent mechanism. Despite the constitutive presence of cytokine transcripts in differentiated cells under steady state conditions, cytokine production is not detectable in the absence of stimulation. Moreover, mature mast cells, basophils, and eosinophils also constitutively express IL-13. Both preformed IL-4 and IL-13 mRNAs are sufficient for rapid cytokine production upon stimulation. Our data show that mast cells, basophils, and eosinophils are programmed for IL-4 and IL-13 expression early in ontogeny. These novel findings have important implications for the prevention and therapeutic intervention of allergic and asthmatic diseases.

Alleles↗
PubMed2005

Identification of antigen-capturing cells as basophils.

Binding of intact Ag is a hallmark of Ag-specific B cells. Apart from B cells, a small number of non-B cells can bind Ag with comparable efficacy as B cells and are found in the peripheral blood, spleen, and bone marrow of mice. This population has been observed for a long time and recently named "Ag-capturing cells." Their identity remained enigmatic. In this study, we show that these cells are basophilic granulocytes. Their ability to capture Ags is dependent on surface IgE receptors and on Ag-specific plasma IgE molecules appearing after immunization. Several surface markers including surface bound IgE, IL-3R, CD45, CD16/32, and the chemokine receptor CCR2 were used to clearly identify these cells. Cross-linkage of surface Igs results in the release of large amounts of IL-4 and IL-6. The data identify basophils as Ag-capturing cells and support the concept of basophils as important regulators of humoral immune responses.

Animals↗
PubMed1999

[Level of histamine in supernatants from the basophil activation test: applications to hymenoptera allergy and drug allergy--preliminary study].

Histamine Release technic consists in calculating histamine liberated by blood cells in touch with an allergen. To this day, this method is only used in Hymenoptera venom allergy diagnosis. The principle of this study is to measure histamine released by activated basophils in surnageons of Basophil Activation Test (BAT) for different allergens: Hymenoptera venoms: Bee, White Faced Hornet, Vespula Wasp. Drugs: Cefaperos, Clamoxyl, Alfatil, Rapifen, Diprivan, Nesdonal, Mivacron. A threshold of positivity (amplification factor in comparison with the control) is determined for these two classes of allergens: 45 for Hymenoptera venoms and 9 for drugs. These results, compared to the other diagnosis technics (Histamine Release, Basophil Activation Test, Prick Tests) discloses very high correlation rates in each case. This method seems to be a reliable method for Hymenoptera venom allergy diagnosis and for drugs allergy diagnosis too. However, this study is based on a few number of patients, so a significant statistic conclusion can't be expressed but it opens an interesting way of research.

Basophil Degranulation Test↗
PubMed1999

The monoclonal antibody 97A6 defines a novel surface antigen expressed on human basophils and their multipotent and unipotent progenitors.

Basophils (Ba) and mast cells (MC) are important effector cells of inflammatory reactions. Both cell types derive from CD34(+) hematopoietic progenitors. However, little is known about the cell subsets that become committed to and give rise to Ba and/or MC. We have generated a monoclonal antibody (MoAb), 97A6, that specifically detects human Ba, MC (lung, skin), and their CD34(+) progenitors. Other mature hematopoietic cells (neutrophils, eosinophils, monocytes, lymphocytes, platelets) did not react with MoAb 97A6, and sorting of 97A6(+) peripheral blood (PB) and bone marrow (BM) cells resulted in an almost pure population (>98%) of Ba. Approximately 1% of CD34(+) BM and PB cells was found to be 97A6(+). Culture of sorted CD34(+)97A6(+) BM cells in semisolid medium containing phytohemagglutinin-stimulated leukocyte supernatant for 16 days (multilineage assay) resulted in the formation of pure Ba colonies (10 of 40), Ba-eosinophil colonies (7 of 40), Ba-macrophage colonies (3 of 40), and multilineage Ba-eosinophil-macrophage and/or neutrophil colonies (12 of 40). In contrast, no Ba could be cultured from CD34(+)97A6(-) cells. Liquid culture of CD34(+) PB cells in the presence of 100 ng/mL interleukin (IL)-3 (Ba progenitor assay) resulted in an increase of 97A6(+) cells, starting from 1% of day-0 cells to almost 70% (basophils) after day 7. Culture of sorted BM CD34(+)97A6(+) cells in the presence of 100 ng/mL stem cell factor (SCF) for 35 days (mast cell progenitor assay) resulted in the growth of MC (>30% on day 35). Anti-IgE-induced IgE receptor cross-linking on Ba for 15 minutes resulted in a 4-fold to 5-fold upregulation of 97A6 antigen expression. These data show that the 97A6-reactive antigen plays a role in basophil activation and is expressed on multipotent CD34(+) progenitors, MC progenitors, Ba progenitors, as well as on mature Ba and tissue MC. The lineage-specificity of MoAb 97A6 suggests that this novel marker may be a useful tool to isolate and analyze Ba/MC and their progenitors.

Animals↗