Cyclooxygenase metabolites in human lung anaphylaxis: Airway vs. parenchyma

We studied the generation of arachidonic acid cyclooxygenase metabolites (AACMs) during in vitro anaphylaxis of passively sensitized human lung parenchymal and airway fragments. Prostaglandins E, F₂(α), D₂, 6-keto-prostaglandin F₁(α), and thromboxane B₂ (PGE, PGF₂(α), PGD₂, 6-keto-PGF₁(α), TXB₂, respectively) were assayed by radioimmunoassay. Results with airway tissue were compared with subpleural parenchymal fragments from the same lungs similarly challenged. Spontaneous generation of prostacyclin (PGI₂), as measured by its stable metabolite 6-keto-PGF₁(α), exceeded by two- to threefold other spontaneous AACM release in both bronchial and parenchymal fragments. In airway antigen produced variable AACM responses, but in general the rank order was 6-keto-PGF₁(α) > PGE is approx. the same as PGF₂(α) > PGD₂ > TXB₂. The rank for antigen-induced AACM release from parenchyma was 6-keto-PGF₁(α) is approx. the same as PGD₂ > > PGF₂(α) > TXB₂ is approx. the same as PGE. In airway, as in parenchyma, very little AACM production during anaphylaxis can be attributed to smooth muscle contraction per se. Histamine released from bronchi (0.67 ± 0.30 μg/g lung) was significantly less than from parenchyma (3.7 ± 0.70 μg/g) despite comparable histamine content. At comparable levels of histamine release, the parenchyma produced greater quantities than bronchi of all AACMs except PGE. The comparatively limited bronchial capacity to generate PGF₂(α), PGD₂, TXB₂, and histamine (airway constrictors) along with predominant generation of PGI₂ and PGE (airway relaxants) may help preserve airway patency.