Asthma: Cells and Cytokines

Abstract

The pathology of bronchial asthma demonstrates a multicellular process. In an attempt to elucidate the cellular biology of airways inflammation, it becomes important to understand not only the biology of each individual cell type but also the interaction between different cells. This review focuses on a documentation of some of the biological effects of the constituent cells in the airway mucosa and a discussion of their potential interactions through the release and action of different cytokines. It seems likely that future research will address the in vivo release of different cytokine molecules in the asthmatic process using techniques of molecular biology. There likely will be increasing information available about the regulation and the actions of these molecules on target cells and tissues. Elucidation of some of the complex interactions between different cells and the role of different cytokine molecules may provide a novel approach to the therapy of bronchial asthma.

Bi-Directional Activation Between Human Airway Smooth Muscle Cells and T Lymphocytes: Role in Induction of Altered Airway Responsiveness

“…Although the mechanistic interplay between airway inflammation and the associated changes in ASM responsiveness remains to be fully characterized, the wealth of evidence accumulated to date suggests that the altered airway responsiveness in asthma is primarily attributed to the actions of various cytokines, which are primarily produced by infiltrating CD4 ϩ T lymphocytes expressing the Th2 profile of cytokine release (1-8, 27, 28). In keeping with this notion, the observed changes in ASM responsiveness in asthmatic individuals and in animal models of allergic asthma have been associated with elevated bronchoalveolar lavage fluid and serum levels of the Th2-type cytokines, notably IL-4, IL-5, IL-13, and GM-CSF (15,16,(27)(28)(29)(30). Moreover, relative to nonatopic, nonasthmatic subjects, mononuclear cells isolated from peripheral blood and bronchoalveolar lavage fluid samples obtained from atopic asthmatic patients have also been found to display enhanced production of these Th2-type cytokines when these cells are activated in vitro, whereas their profile of Th1-type cytokine expression is suppressed (30,31).…”

Autologously up-regulated Fc receptor expression and action in airway smooth muscle mediates its altered responsiveness in the atopic asthmatic sensitized state

“…Allergic asthma is characterized by increased airway reactivity to bronchoconstrictor agonists, impaired ␤-adrenoreceptormediated airway relaxation, and inflammation of the airways (11,12,29). The altered airway responsiveness in asthmatic individuals has been associated with elevations in total and antigen-specific serum IgE (30,31).…”

“…In individuals with atopic asthma, mast cell activation has been implicated in mediating the immediate bronchoconstrictor response acutely following antigen inhalation, a process involving IgE-mediated activation of the high affinity IgE receptor (FcRI), leading to cellular degranulation and the release of various mast cell-derived mediators (4)(5)(6). The identification of Fc receptors on other cell types in the lung (e.g., mononuclear cells, eosinophils, and dendritic cells) suggests that, apart from mast cells per se, these other cell types may also serve to propagate the pro-inflammatory allergic pulmonary response, most likely via the orchestrated extended release of various cytokines (7)(8)(9)(10)(11)(12)(13). Accordingly, immune complex͞Fc receptor interactions potentially underlie the progression of the airway inflammatory and bronchoconstrictor responses in asthma, wherein the immediate bronchoconstriction accompanying antigen exposure is followed by the development of the late phase asthmatic response involving various proinflammatory cells.…”

Airway Inflammation and Structural Changes in Airway Hyper‐Responsiveness and Asthma: An Overview

“…Furthermore, a variety of structural alterations have been reported, including goblet cell hypertrophy, smooth muscle hypertrophy or hyperplasia and extracellular matrix modifications, including subepithelial fibrosis (8,10,12). These inflammatory and structural changes probably result from complex positively or negatively orchestrated mechanisms in tissues, including structural cell-immune cell communications via cell-cell contacts, mediator-and cytokine-driven messages and cell-extracellular matrix interactions (26)(27)(28)(29). PLASMA TRANSUDATION AND AIRWAY WALL THICKNESS Plasma transudation may contribute to the increased airway response (25,30).…”