The cardinal importance of sputum microscopy.
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Asthma↗
Biomedical subjects
T T Hansel
Publications and source records attributed to T T Hansel.
Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia.
Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.
Adult↗
Human peripheral blood eosinophils produce and release interleukin-8 on stimulation with calcium ionophore.
We present evidence that human blood eosinophils produce interleukin (IL)-8 when stimulated with calcium ionophore. Following in vitro culture of 99% pure eosinophils with calcium ionophore, released IL-8 was detectable by enzyme-linked immunosorbent assay in supernatants. Eosinophil IL-8 production was considerably greater than that of IL-3 or granulocyte macrophage colony-stimulating factor. Furthermore, eosinophil production of IL-8 in the presence of calcium ionophore could be inhibited with the immunomodulating agent cyclosporin A and the protein synthesis inhibitor cycloheximide. In addition, following stimulation of highly purified blood eosinophils with calcium ionophore, IL-8 mRNA was detectable after polymerase chain reaction amplification. In comparison with other cells on stimulation with calcium ionophore, eosinophils produce about half as much IL-8 as neutrophils but significantly more than purified T cells. In contrast to monocytes and neutrophils, IL-8 production was not inducible with IL-1 or tumor necrosis factor. Finally, following calcium ionophore stimulation blood eosinophils were shown to contain cytoplasmic IL-8 by employing a monoclonal antibody against IL-8 in conjunction with immunohistochemistry. These observations demonstrate that eosinophils are capable of IL-8 production and release, which may contribute to defense against parasites and to the pathophysiology of allergic and asthmatic disease.
Calcimycin↗
Eosinophils and cytokines.
Cytokines act on eosinophils to regulate eosinophil function, with IL-5 recognised to be especially important in control of eosinopoiesis, eosinophil survival and eosinophil priming. In addition, eosinophils have the capacity to produce cytokines involved in acute and chronic inflammatory and repair processes, as well as to produce cytokines that stimulate eosinophils within an autocrine loop. This paper describes (A) an immunomagnetic selection technique for the purification of human blood eosinophils, and (B) a method that employs immunofluorescence with flow cytometry for measurement of blood and sputum eosinophil surface markers. Having demonstrated that sputum eosinophils express HLA-DR, highly purified blood eosinophils were used to analyse (C) the induction and function of eosinophil HLA-DR. Cytokines have the capacity to induce eosinophil HLA-DR, and are produced by eosinophils as an accessory function during antigen presentation. Finally, preliminary data on (D) eosinophil production of IL-8 is presented. Hence, eosinophils have the capacity to act as immunomodulatory cells within cells networks in allergic and asthmatic inflammation.
Antigens, Surface↗
(+/-) isoprenaline revisited: adverse effects of sympathomimetics in asthma.
It is a matter of concern that regular, excessive use of contemporary sympathomimetics has been associated with morbidity and mortality from asthma. As a consequence, restrictions on sympathomimetic usage have recently been advocated in asthma management guidelines. he association between excessive use of inhaled (+/-)isoprenaline and an epidemic of asthma deaths in the 1960s provides a precedent; hence, we have reviewed the numerous clinical and experimental reports concerning (+/-) isoprenaline to provide insight into the present controversy.
Asthma↗
Anomalous bronchospasm following inhalation of (+) isoprenaline by asthmatics.
Sympathomimetics (beta-adrenergic agonists) presently used in asthma therapy comprise racemic mixtures of bronchodilator and non-bronchodilator enantiomers. In a randomized, double-blind placebo-controlled study, asthmatic subjects inhaled a nebulized solution of the non-bronchodilator (+) enantiomer of isoprenaline. Substantial decreased forced expiratory volume (FEV1) was detected in 2 patients and of the remaining 8, a single subject had increased reactivity to histamine 7 h after inhalation of (+) isoprenaline. These effects of (+) isoprenaline may contribute to anomalous effects of (+/-) isoprenaline in asthma.
Administration, Inhalation↗
Sinus computerized tomography in primary hypogammaglobulinaemia.
Thirteen patients suffering from primary hypogammaglobulinaemia receiving intravenous immunoglobulin replacement therapy underwent computerized tomography of the paranasal sinuses. The CT scans were evaluated and related to clinical data from the patients, who were selected for study on the basis of having symptoms of rhinosinusitis. The scans varied from normal to demonstrating widespread sinus abnormality. There was no relationship between the scan findings and duration of ENT symptoms, range of current symptoms, or the interval between the onset of ENT symptoms and the start of intravenous immunoglobulin replacement therapy. It is nevertheless possible that prompt institution of replacement therapy, after correct diagnosis early in the course of the disease, may prevent the development of sinus disease refractory to such treatment.
Adolescent↗
Induction and function of eosinophil intercellular adhesion molecule-1 and HLA-DR.
We have previously established that eosinophils studied ex vivo from the sputum of asthmatics express intercellular adhesion molecule-1 (ICAM-1) and HLA-DR, whereas peripheral blood eosinophils do not express these surface proteins. On incubation of highly purified (greater than 99.5% pure) blood eosinophils from normal subjects with T cell supernatants, eosinophil ICAM-1 was induced in 24 h, whereas HLA-DR was maximally induced within 48 h. Recombinant cytokines that enable eosinophil survival (IL-5, IL-3, and granulocyte macrophage-CSF) were found to be unable to induce ICAM-1 or HLA-DR, even when pooled at concentrations individually required for eosinophil survival. However, synergy between these eosinophil survival factors and TNF (-alpha and -beta) was found mainly responsible for ICAM-1 induction, whereas synergy between IL-3 and IFN-gamma occurred for HLA-DR induction. Culture of eosinophils in the presence of cytokines and cycloheximide prevented expression of ICAM-1 and HLA-DR, showing that de novo eosinophil protein synthesis is occurring. At a functional level we demonstrate that ICAM-1-bearing eosinophils have increased adhesion capacity for autologous T cells. In contrast, HLA-DR-expressing eosinophils mediated Ag-specific proliferation of an autologous HLA-DR-restricted T cell clone that was inhibitable by anti-HLA-DR and anti-ICAM-1 mAb. Since eosinophil-mediated Ag presentation was inhibitable by treatment of eosinophils with glutaraldehyde or chloroquine, this suggests that eosinophils participate in Ag uptake, processing, and presentation and have accessory functions. Thus, through the induction of ICAM-1 and HLA-DR on tissue eosinophils, eosinophils have the capacity to interact with leukocytes and present Ag to T cells.
Antigen-Presenting Cells↗
The role of T lymphocytes in the pathogenesis of asthma.
Recently there have been advances in our understanding of the role of thymic (T) lymphocytes in asthma. In this brief review we discuss evidence for T cell involvement in asthma, with emphasis on T cell surface markers associated with activation and T cell production of cytokines. We proceed to describe how T cells influence inflammatory effector cells such as mast cells and eosinophils. However, mast cells and eosinophils are also capable of cytokine production, and participate in inflammatory cell networks within the bronchial tissue of asthmatics.
Asthma↗
The migration of eosinophils into the sputum of asthmatics: the role of adhesion molecules.
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Asthma↗
Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage.
Activation of lymphocyte subpopulations was determined in conjunction with levels of cytokines in peripheral blood and bronchoalveolar lavage (BAL) of asthmatics. Allergic asthmatics had increased numbers of CD4+ IL-2R+ T cells in peripheral blood and BAL, and T-cell activation closely correlated with numbers of low-affinity IgE receptor (CD23) bearing B cells. In contrast, in nonallergic asthmatics both CD4+ and CD8+ T cells from blood and BAL had increased expression of IL-2R, HLA-DR, and VLA-1. Furthermore, in the nonallergic asthmatics CD8+ T cells were decreased in blood but increased in BAL. Cytokine levels were determined in BAL fluid and supernatants from purified peripheral blood T cells and enriched BAL lymphocyte preparations. Allergic asthmatics were characterized by increased levels of IL-4 and IL-5, and this elevated IL-4 contributed to the elevated IgE levels found in these allergic subjects. In contrast, nonallergic asthmatics had elevated levels of IL-2 and IL-5, with IL-2 contributing to T-cell activation. In both types of asthma, the close correlation of IL-5 levels with eosinophilia suggests that IL-5 is responsible for the characteristic eosinophilia of asthma. Thus, we provide evidence of distinct T-cell activation resulting in different spectra of cytokines in allergic and nonallergic asthma.
Adolescent↗
An improved immunomagnetic procedure for the isolation of highly purified human blood eosinophils.
A simple method is described for the isolation of human peripheral blood eosinophils by an immunomagnetic procedure. Superparamagnetic particles were coupled to a monoclonal antibody against CD16, a molecule present on neutrophils but not on eosinophils. A peripheral blood granulocyte preparation, containing neutrophils and eosinophils, was incubated with these anti-CD16 particles. In the magnetic field of a permanent magnet, magnetically labelled neutrophils were then retained on columns with a ferromagnetic matrix. By this negative selection procedure, eosinophils of 99.5% purity were obtained from normal individuals and 99.6% purity from patients with eczema. A comparison was made between the immunomagnetic method and eosinophil isolation after N-formyl-methionyl-leucyl-phenyl-alanine treatment. Even in the case of individuals with very low eosinophil counts, the immunomagnetic method permits the efficient isolation of highly purified and functionally active eosinophils.
Antigens, CD↗
Sputum eosinophils from asthmatics express ICAM-1 and HLA-DR.
Sputum from symptomatic asthmatics is a rich source of eosinophils from the respiratory tract. Following liquefaction of sputum with dithioerythritol (DTE), a cell suspension for indirect double immunofluorescence with flow cytometry was obtained. Eosinophils were identified using anti-CD9 fluorescein conjugate, and particular surface markers measured with the relevant mouse MoAb followed by goat anti-mouse immunoglobulin phycoerythrin conjugate. Blood and sputum eosinophil surface markers were determined in parallel from asthmatics not receiving steroid therapy. Sputum eosinophils were found to have considerably elevated levels of CD11b, a reflection of eosinophil activation. Sputum but not blood eosinophils were found to express ICAM-1 (nine out of 11 cases) and HLA-DR (eight out of 11 cases). Furthermore, following culture of normal blood eosinophils with pooled T cell supernatants, ICAM-1 and HLA-DR could be induced in vitro. The induction of eosinophil adhesion molecules such as ICAM-1 and HLA-DR may influence eosinophil localization and function in asthma.
Antigens, CD↗
Immunohistochemical demonstration of CD23 expression on lymphocytes in rheumatoid synovitis.
The leucocyte antigen CD23 is expressed by B lymphocytes following activation by a number of stimuli and functions as an IgE receptor, and in its soluble form, as a putative B cell growth factor. The expression of CD23 on the surface of lymphocytes in paraffin wax sections of synovial biopsy specimens was studied using a novel mouse monoclonal antibody, BU38. Specimens were investigated from nine cases of rheumatoid arthritis, six cases of osteoarthritis, and eight cases of chronic inflammation in articular and non-articular tissues. CD23 was expressed on a high proportion of lymphocytes in all forms of chronic inflammation and was not specific for rheumatoid arthritis. It may be a characteristic feature of any chronic inflammatory response. As CD23 was found on the surface of lymphocytes in many cases of these arthritides, sCD23 in serum or synovial fluid may yet prove a useful marker for the severity of the inflammatory infiltrate.
Adolescent↗
Granulomatous enteropathy in common variable immunodeficiency: a cause of chronic diarrhoea.
Gastrointestinal disease is a well recognized feature in patients with common variable immunodeficiency, and is often due to infection with a variety of organisms. Symptoms usually improve with appropriate antibiotic therapy and replacement gammaglobulin. We describe three middle-aged female patients with common variable immunodeficiency who had protracted diarrhoea and weight loss. Despite extensive investigation no infectious cause was found. All patients had granulomas distributed throughout the gastrointestinal tract, but no features of inflammatory bowel disease. There was a poor response to gammaglobulin replacement therapy, antibiotics or symptomatic treatment. We suggest that granulomatous enteropathy is another gastrointestinal manifestation of common variable immunodeficiency.
Adult↗
Isolation of eosinophils from human blood.
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Cell Adhesion↗
Immunohistochemical determination of CD23 expression in Hodgkin's disease using paraffin sections.
The leukocyte antigen CD23 is expressed during B-cell development, and functions as an IgE receptor and a lymphocyte growth factor. We studied the expression of CD23 in paraffin sections of lymphoid tissue using the monoclonal antibody BU38. Fifteen cases of Hodgkin's disease, ten reactive lymph nodes, eight B-cell, and seven T-cell non-Hodgkin's lymphomas were analysed immunohistologically. CD23 positivity was seen on follicular dendritic cells and a small number of lymphocytes in reactive nodes. Thirteen of the 15 cases of Hodgkin's disease showed CD23 expression in both neoplastic cells and reactive lymphocytic infiltrate. The antigen was demonstrated in four of the B-cell and one of the T-cell tumours. CD23 may be important in mediating the mixed cellular infiltrate characteristic of Hodgkin's lymphoma.
Adolescent↗
IgE: an immunoglobulin specialized in antigen capture?
IgE bound to the low-affinity receptor for immunoglobulin E (Fc epsilon R) on antigen-presenting cells (APCs) may permit binding of antigens to APCs prior to their processing and presentation. Here, G. C. Mudde and colleagues argue that the unique characteristics of IgE serological responses together with the distribution of Fc epsilon RII (CD23) on APCs are consistent with this novel function of IgE. The concept of IgE involvement in antigen capture is discussed in relation to Langerhans cells, B cells and follicular dendritic cells.
Animals↗