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Conrad Notes IndexspacerAllergy, Asthma, and Immunology Index

Conrad Notes
a timely medical meeting newsletter
C. E. Reed, MD, Mayo Clinic, Rochester, Minn, clarified the role of eosinophils, lymphocytes, mast cells, and cytokines in the pathogenesis of asthma. Understanding the language of the cellular and molecular biologist will result in a better grasp of the disease and improve patient management. The current explosion of information carries the need for periodic review, evaluation, and consolidation.
Cytokines A cytokine is a regulatory protein secreted by one cell that controls survival, growth, differentiation, and functions of another cell. Cytokines affect the cell nucleus to cause DNA transcription rather than change the cell membrane or cytoplasm.
Eosinophils in asthma Bone marrow precursors of the eosinophil undergo growth and development as determined by locally produced cytokines. Interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony stimulating factor (GMC-SF) participate in the maturation process.

Upon entering the circulation, mature eosinophils undergo activation by the above-specified cytokines. Activation leads to synthesis of new cell surface proteins, including adhesion molecules. Next, chemoattractant agents, reacting with cell surface receptors, bind to endothelial cells. This interaction causes the activated eosinophil to be pulled across the endothelium into bronchial tissue. In addition, more eosinophils become activated.

Activated eosinophils produce leukotrienes and cytokines including IL-5. In the final step, tissue eosinophils stimulated by as yet incompletely defined agents, including IgG, and abetted by IL-5, undergo degranulation. This process releases major basic protein (MBP), eosinophil cationic protein (ECP), peroxidases and other proteins. The products of degranulation lead to local tissue damage, allergic rhinitis, and asthma.

IL-5 is especially important in asthma. This interleukin helps in the maturation, activation, and degranulation of the eosinophil. In addition, IL-5 enhances the longevity of eosinophils.

Mast cells in asthma The response to inhaled allergen can be separated into the immediate and late allergic reactions, IAR and LAR. Immunologic activation of the mast cell during IAR leads to degranulation and release of histamine and arachidonic acid metabolites. The latter include the leukotrienes. During LAR, several interleukins (IL-3, -4, -5, and -6), GM-CSF, and interferon gamma (INFg) result from antigen-induced DNA transcription. Mast cells account for 30 percent and lymphocytes for 70 percent of the cytokines involved in asthma.
Allergic vs nonallergic asthma Eosinophilia, bronchial hyperresponsiveness, and IL-5 production characterize both types of asthma. In allergic asthma, IL-4 is responsible for the initiation and perpetuation of IgE antibody production by B lymphocytes. Bronchoalveolar lavage (BAL) samples show that IL-2, instead of IL-4, is present in nonallergic asthma. IL-2 stimulates other lymphocytes such as CD8+ and natural killer (NK) cells to produce IL-5.

T lymphocyte subsets also help differentiate the two types of asthma. Activated CD4+ helper cells, producing IL-4 and IL-5, along with TH2-like cells, are present in BAL fluid from allergic, but not from nonallergic, asthma patients. Activated CD8+ cytotoxic cells and NK cells characterize BAL fluid from patients with nonallergic asthma.

In summary Cytokines play an important role in the pathogenesis of asthma:

  • Mast cells produce TH2-like cytokines, especially IL-5, the most important and specific cytokine.

  • Macrophages, the first cells to meet the antigen, release many cytokines to initiate and perpetuate asthma.

  • Activated eosinophils release toxic granule proteins resulting in bronchial tissue damage, allergic rhinitis, and asthma.

Eugene A. Conrad

Presented at the Annual Meeting of the American College of Allergy, Asthma and Immunology on 9 November 1996
CONRAD NOTES, © January 1997 All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078 / posted 8-Feb-1997

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