Mechanisms of asthma and allergic inflammation
Allergy and asthma

https://doi.org/10.1016/j.jaci.2005.02.032Get rights and content

Initiation and regulation of allergic inflammation is influenced by many factors, including cell type, membrane receptors, and mediators generated. Furthermore, the altered response of targeted tissues (ie, airway smooth muscle) becomes important to the eventual expression of asthma. Finally, the genetic regulation and association of genetic polymorphisms has enhanced our understanding of host susceptibility. In this review key findings published in 2004 issues of the Journal of Allergy and Clinical Immunology are highlighted to demonstrate recent advances in these areas.

Section snippets

Eosinophil biology

If the years 2002 and 2003 signaled the death of the eosinophil in asthma, then 2004 was a comeback year. The exact role of the eosinophil in asthma and other allergic diseases remains somewhat controversial, but numerous articles in the JACI and elsewhere continue to provide interesting information on eosinophil biology and its potential relevance to diseases such as asthma.

Given the selective expression of the chemokine receptor CCR3 on eosinophils, Radinger et al,1 using the BALB/c ovalbumin

Mast cells and basophils

Since its US Food and Drug Administration approval and introduction to the market in September 2003, omalizumab (Xolair; Novartis, Genentech Pharmaceuticals) provides the latest option for management of moderate-to-severe persistent asthma. In addition to its direct ability to block IgE attachment to FcεRI, studies uncovered a remarkable ability of IgE to regulate surface expression of its own receptor.10 This initial report suggested the effect on circulating basophils was rapid and complete

Contribution of smooth muscle cells to airway inflammation in asthma

A model of the contribution of smooth muscle cells to airway inflammation in asthma is shown in Fig 1. Airway inflammation is a characteristic feature of asthma and likely contributes to both airway obstruction and airway hyperresponsiveness. Although many factors contribute to airway inflammation, studies to date have largely focused on the effect of cells recruited to the airway and their activation and release of inflammatory mediators to cause pulmonary dysfunction. During the past year,

Cysteinyl leukotrienes

A model of the role of cysteinyl leukotrienes in the generation of allergic inflammation is shown in Fig 2. To further understand the complexity and contribution of cysteinyl leukotrienes to processes of airway inflammation in asthma, Parameswaran et al27 at McMaster University evaluated the effect of the leukotriene receptor antagonist pranlukast on allergen-induced changes in circulating dendritic cells in patients with mild asthma. Blood samples were obtained before and 3 and 24 hours after

Nitric oxide

Nitric oxide (NO) generation is associated with ongoing airway inflammation. Measurements of exhaled nitric oxide (eNO) have begun to serve as a biomarker for the presence of airway inflammation, and a reduced eNO level is an indicator of positive responses to anti-inflammatory medications, such as corticosteroids. Mahut et al29 evaluated levels of eNO in 28 children with refractory asthma, which they defined as persistent airflow limitation, or exacerbations, despite the use of high-dose

T cells in asthma

Using a rodent model, Isogai et al31 evaluated the hypothesis that T cells might migrate from the airways to the bone marrow to stimulate cells at this location and thus perpetuate the inflammatory response. Using the Brown Norway rat, the investigators introduced purified fluorescein-labeled CD4+ T cells into the trachea of naive or sensitized animals. Eighteen hours later, the rats were challenged with antigen, and cells were then harvested from the bone marrow, BAL fluid, lungs, lung blood

Genetics

The association of genes and their polymorphisms with features of asthma has been an important advance over the past decade. Last year saw a number of studies that evaluated the associations of various genes with features of asthma. As noted in a number of these articles, replication of earlier reports is essential to confirm these genetic associations. From these studies, it has also become apparent that different populations of patients might have different asthma characteristics, and the

Conclusions

Our understanding and appreciation of allergic cellular events and their integration into diseases like asthma continues to expand. Although these processes appear complex and sometimes independent when presented as single articles, their contribution to the overall theme of allergic diseases becomes more apparent when looked at over a longer time period, such as the past year. The JACI has been pleased to provide its readers with new and key observations that help to fit the puzzle together

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    Disclosure of potential conflict of interest: B. Bochner is a paid consultant for Amgen, Aventis, and GlaxoSmithKline and a codiscoverer with GlaxoSmithKline of Siglec-8, for which they share a patent; he is on the Speakers' Bureau for Merck, Genentech, and Novartis; and he is on advisory boards for Pfizer and Glycomimetics, Inc. W. W. Busse has consultant arrangements with Bristol-Meyers Squibb, Dynavax, Hoffman Laroche, and Fujisawa; has received grants–research support from GlaxoSmithKline, Fujisawa, Aventis, Hoffman Laroche, and Pfizer; is on the speakers' bureau for Merck, GlaxoSmithKline, and Aventis; and is on advisory boards for GlaxoSmithKline, Aventis, Pfizer, and AstraZeneca.

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