Fragments of human lung parenchyma were passively sensitized with ragweed IgE in vitro, and subjected to antigenic challenge in experiments designed to explore the genesis of arachidonate metabolites during lung anaphylaxis. Lung supernatant was sampled serially and examined for histamine as a marker of mast cell activation, and prostaglandins E 2, F(2α), and 13,14-dihydro, 15-keto-PGF(2α). In eight of nine human lung experiments, the kinetics of PGE 2 and PGF(2α) production were indistinguishable from that of histamine release. In all experiments PGF(2α) production (40.7 ± 7.1 ng PGF(2α)/g of lung tissue) was large compared with PGE production (4.0 ± 1.0 ng PGE/g of lung tissue). When lung fragments were challenged with high concentrations of 3 smooth muscle contractants (histamine, methacholine, and KCl), PGF(2α) production was only 5 to 20% of that seen with optimal antigenic challenge of the same tissue. On this basis we concluded that neither released histamine, either directly or indirectly, nor smooth muscle contraction per se was primarily responsible for the large PGF(2α) production during lung anaphylaxis. Passively sensitized human bronchial tissue was evaluated in an organ bath for PGF(2α) and PGE production and tension development after sequential challenge with histamine (10 -4 M), methacholine (10 -4 M), and optimal dose antigen. In contrast to lung parenchyma, for sensitized bronchial tissue, (a) PGE production predominated as much as fivefold over PGF(2α) production after challenge with each of the 3 stimuli, and (b) the quantity of PGF(2α) produced was similar in some but not all lung specimens for antigen challenge as for challenge with histamine or methacholine. We concluded that in bronchi, unlike that in parenchyma, PGE and PGF(2α) production may be largely accounted for in some but not all lung specimens by the effect of spasmogenic mast cell mediators, such as histamine, on smooth muscle or associated tissues. Based on these observations and published data, it seems unlikely that the mast cell itself is a major source of the bronchospastic PGF(2α) production during anaphylaxis in lung parenchyma. The most likely origin of the PGE(2α) is an undetermined cell type (or types) that is relatively abundant in lung parenchyma compared with that in bronchial tissue. The secondary stimulus for PGF(2α) production during lung anaphylaxis remains unknown.
|Original language||English (US)|
|Number of pages||10|
|Journal||American Review of Respiratory Disease|
|State||Published - Jul 25 1980|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine