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Role of leukotrienes in bronchial hyperresponsiveness and cellular responses in airways
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  1. Alan R Leff
  1. Department of Medicine, Pediatrics, Pharmacological and Physiological Science, Anesthesiology and Critical Care, Committees of Cell Physiology and Clinical Pharmacology and Section of Pulmonary and Critical Care Medicine, The University of Chicago, Chicago, IL 60637, USA
  1. Dr A R Leffaleff{at}medicine.bsd.uchicago.edu

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Among constitutively present cells, bronchoactive leukotrienes are produced predominantly by mast cells1 and macrophages.2 A unique characteristic of asthmatic inflammation is the migration of leukocytes from the peripheral blood to the conducting airways of the lung. This is especially true of the eosinophil, which is not present in the airways of normal individuals, but may be found in massive numbers during periods of airway hyperresponsiveness in asthmatic individuals (fig1).3-5 Most experimental models indicate that eosinophils are an invariable component of asthmatic hyperresponsiveness, although some studies suggest that bronchoconstriction can occur in the relative absence of these cells.

Figure 1

Effect of eosinophil infiltration into human airways. At later stages a cytotoxic effect probably accounts for the epithelial denudation found in human asthma. (A) Histological section of the airway of a patient with asthma (stain: haematoxylin-eosin; original magnification ×160). (B) Same section stained with fluorescent monoclonal antibody for the eosinophil major basic protein (MBP; magnification ×160). (C) Higher power view of the desquamated epithelium in (A) (basal magnification ×400). (D) Localisation of MBP in cells (arrowheads); these cells correspond directly to the cells marked in (C). MBP is also localised outside cells in association with epithelial desquamation (arrow; original transformation ×400). (C) and (D) illustrate the identical area; this section was first stained for MBP by immunofluorescence and subsequently stained with haematoxylin-eosin. Reprinted with permission from Gleich.5

For the purposes of this discussion, the eosinophil will be viewed as a leukotriene transport system capable of providing a substantial reservoir of bronchoactive leukotrienes to airways in relatively short time. They may be delivered to conducting airways in large numbers and have the capacity to produce cysteinyl leukotrienes (LTC4) which cannot be produced by neutrophils, but also migrate into conducting airways in some circumstances.6 7 This discussion …

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