Basic mechanisms in asthma.
In summary, mast cell activation is associated with the release of chemotactic factors, enzymes, proteoglycans, and vasoactive mediators. The vasoactive mediators include the leukotrienes, prostaglandin PGD2, adenosine, PAF, and histamine. Their effects are associated with an early phase reaction. This early reaction in the airways is manifested by cough, wheeze, mucous secretion, and a short-lived bronchospastic response. The release of chemotactic factors perhaps including PAF, eosinophil-directed and neutrophil-directed mediators would be associated with the influx into the airway of a variety of leukocytes although neutrophils and eosinophils predominate. The eosinophil contains a variety of toxic materials including a major basic protein known to kill tracheal epithelial cells. The eosinophil also generates PAF and leukotrienes. It could, therefore, be responsible for a self-sustaining tissue damaging inflammatory infiltrate. And finally, there are the neutral protease enzymes whose function remains unknown. It is tempting to speculate that the vasoactive mediators cause an early phase reaction while the enzymes and chemotactic factors set up the inflammation associated with a late phase response. The clinical pertinence to this has been demonstrated by researchers who studied nonspecific bronchial reactivity in patients who have early phase reactions only as compared with those who have both early and late phase reactions to antigen bronchoprovocation. These individuals with only an early phase reaction following antigen bronchoprovocation have a lesser degree of sensitivity to histamine, ie, it requires more histamine to cause bronchoconstriction, and there is no change in their histamine threshold after their early phase response.(ABSTRACT TRUNCATED AT 250 WORDS)
Wasserman
S I
SI
University of California Medical Center, San Diego 92103.
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000008:administration & dosage; D001249:Asthma / Q000503:physiopathology*; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects; D001986:Bronchial Spasm / Q000209:etiology; D006801:Humans; D008168:Lung / Q000473:pathology; D008407:Mast Cells / Q000201:enzymology / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology; D010972:Platelet Activating Factor / Q000502:physiology; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000502:physiology; D012137:Respiratory System / Q000473:pathology; D013189:SRS-A / Q000502:physiology; D012867:Skin / Q000473:pathology
D000485:Allergens; D009479:Neuropeptides; D010972:Platelet Activating Factor; D011457:Prostaglandins D; D013189:SRS-A; D015230:Prostaglandin D2