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Granulocyte-macrophage colony-stimulating factor (GM-CSF), a 23-kDa polypeptide, was originally identified as a hematopoietic growth factor, but has recently been found to be a multifunctional cytokine with many proinflammatory activities (1,2). GM-CSF can be produced by, and a ...

In addition to being essential for differentiation and maturation, regulated gene expression governs many cellular responses to their local environment. For example, cytokines, viral infection, and numerous other inflammatory stimuli elicit the expression of specific resp ...

Inflammation of the airways is considered to be the key pathogenetic factor in asthma, airway hyperreactivity and clinical symptoms are considered secondary

To determine the function of a particular cell type, it is necessary either to have a large number of similar (ideally identical) cells or to use extremely sensitive methods to detect the activity of a single cell. Lymphocytes present special difficulties, because they have very precise antigen ...

Adhesion molecules are receptors found on the surface of leukocytes and endothelial cells, which bind to their ligands, either on other cells or on the extracellular matrix. The function of adhesion molecules is to allow leukocytes to interact with other hemopoetic cells or with foreign ant ...

Cytokines are important biochemical mediators essential in initiating and maintaining inflammatory reactions associated with allergic disease in man. Although cytokines can be secreted from a variety of different cell types, considerable attention has been focused on T-lym ...

β2-adrenergic receptor agonists (β-agonists) are first-line agents for the treatment of acute bronchospasm. These drugs achieve bronchodilation primarily via activation of β2-adrenergic receptors (β2AR) located on airway smooth muscle cells. In addition, β-agonists may all ...

Polymorphisms of the β2-adrenoceptor (β2AR) have been the focus of much interest as part of the search to elucidate the genetic basis of asthma and allergic disease. More recently, these polymorphisms have also been implicated in the genetic etiology of essential hypertension (1,2) and obes ...

The condition termed “asthma” has been difficult to define satisfactorily. Much of this problem arises from poor understanding of its causes, natural history, and pathophysiology, and also from a lack of a specific marker(s) of the disease. To the clinician, the diagnosis of asthma is not diffic ...

β-Adrenoceptors (βAR) are members of the G-protein-coupled receptor superfamily, consisting of three subtypes: β1, β2, and β3 (1). cDNAs and genes encoding three subtypes have been cloned from several species, including human. There are only β1- and β2ARs to be found in lung (2), which regulate many ...

In the resting cell, DNA is tightly compacted to prevent transcription factor accessibility. During activation of the cell, this compact inaccessible DNA is made available to DNA-binding proteins, thus allowing the induction of gene transcription (1 ,2). DNA is packaged into chromatin, a h ...

This chapter describes a chemical method for mutational analysis of the human glucocorticoid receptor (hGR) cDNA. Corticosteroid-resistant (CR) asthma is associated with in vitro and in vivo defects in mononuclear cell function (1). In addition, molecular studies using these cells h ...

In addition to important environmental factors, it is now well established that genetic factors contribute significantly to the development of asthma and atopy, accounting for between 30 and 60% of the predisposition (1-3). This genetic predisposition is likely to result from the inheri ...

Stimulation by catecholamine agonists of the β-adrenergic coupled adenylyl cyclase (βAR-AC) system, expressed on human tracheobronchial epithelial cells (ECs), elicits a variety of cellular responses that favorably affect airway function, the intensity of the inflammatory ...

The plasticity of conducting airway epithelia is well recognized (1–3). Under normal conditions, the epithelia express mucociliary function, which is the first pulmonary defense mechanism against inhaled air pollutants. Aberrance in this function is either the cause or one of the major ...

Asthma is considered an airway inflammatory disorder characterized by variable airflow obstruction and airway hyperresponsiveness (1). The inflammatory component of asthma has been studied extensively over the past few years, but, more recently, the potential contribution of ...

Peripheral blood monocytes (PBMs) and alveolar macrophages (AMs) are widely recognized as cells that play a central role in the regulation of immune and inflammatory activities, as well as in tissue remodeling. The fulfillment of these activities is mediated by complex and multifactori ...

Pulmonary monocytes and macrophages are believed to function in a wide range of biological roles, including host defense against foreign organisms, maintenance of immunological homeostasis in the lung, presentation of antigen to lymphocytes, and migration to sites of tissue injury ...

The mitogen-activated protein kinases (MAPK) are an expanding family of proline-directed serine/threonine kinases that are activated, following their dual phosphorylation at conserved threonine and tyrosine residues, by a family of MAPK kinases (MEK). Presently, the MAPK fami ...

Eosinophils have been implicated in allergic diseases, such as bronchial asthma, which is characterized by elevated eosinophil numbers in the bronchoalveolar lavage fluid and peripheral blood. Their accumulation and activation within the airway mucosa is thought to cause tissue ...