Inflammation and cell-cell interactions in airway hyperresponsiveness
| Autor: | Alan R. Leff, C. D. Wegner, K. J. Hamann |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Pulmonary and Respiratory Medicine
Integrins Physiology Molecular Sequence Data Respiratory System Inflammation Cell Communication Granulocyte Models Biological Ribonucleases Sequence Homology Nucleic Acid Physiology (medical) medicine Animals Humans Amino Acid Sequence Base Sequence biology Cell adhesion molecule Eosinophil Granule Proteins business.industry Blood Proteins Cell Biology respiratory system Eosinophil respiratory tract diseases Eosinophils medicine.anatomical_structure Immunology Respiratory Physiological Phenomena Major basic protein biology.protein Respiratory epithelium Bronchoconstriction medicine.symptom business |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 260:L189-L206 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | Airway hyperresponsiveness results from the conversion of normally reactive airways to a state of augmented responsiveness to constrictor stimuli. Although the mechanism accounting for the induction of airway hyperresponsiveness remains elusive, recent investigations have suggested that inflammation may be a sine qua non for human asthma. Numerous experimental models have demonstrated the necessity of circulating granulocytes as mediators of augmented bronchoconstriction during immune challenge. It is not known how granulocytes are targeted for selective migration to the conducting airways of the lung during hyperresponsive states; however, recent evidence implicates the upregulation of granulocyte adhesion molecules on both the endothelial and epithelial surfaces of the airway. There is evidence that during migration diapedesis, granulocytes interact with epithelial and endothelial cells to produce regionally secreted mediators that upregulate the responsiveness of adjacent airway smooth muscle and/or cause lumenal edema, thus augmenting the effect of constrictor stimuli. Most evidence suggests that the eosinophil is the most important granulocyte in these responses and that eosinophilic infiltration and activation may account for the unique, spasmodic, and cyclic nature of hyperreactive airways. The molecular biology of the eosinophil granule proteins has characterized four distinct substances, each of which exerts potential cytotoxic effects on airway epithelium by different mechanism. In addition, at least one of these proteins, the major basic protein, appears to cause direct, noncytotoxic stimulation of epithelial secretion that upregulates nonspecifically the response of airway smooth muscle to contractile stimuli. The recognition of inflammation as the essential component to airway hyperresponsiveness provides a fresh approach to a difficult problem and suggests a host of novel therapies for human asthma. |
| Databáze: | OpenAIRE |
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