In vitro modulation of the eosinophil-dependent enhancement of the permeability of the bronchial mucosa.
1. Basolateral to apical albumin flux has been measured in sheets of bovine bronchial and tracheal mucosa mounted in vitro. 2. Addition of guinea-pig peritoneal eosinophils or neutrophils to the basolateral side of such tissues had no significant influence on the transmucosal flux of albumin in either the bronchial or tracheal mucosa. 3. Stimulation of eosinophils or neutrophils by the calcium ionophore A23187, or by their presentation to an opsonized airways mucosa, resulted in a significant increase in the transbronchial flux of albumin. This effect was seen after only 60 min incubation of the leucocytes with the bronchial mucosa, and was no greater when the contact time was extended to 180 min. Incubation of bronchial mucosal tissues with 1 mg ml-1 polyarginine for 3 h produced a significant increase in albumin flux, but was ineffective at 0.5 mg ml-1. 4. In contrast to the bronchial mucosa, the tracheal mucosa appeared resistant to the effects of stimulated eosinophils and neutrophils. 5. The lipoxygenase inhibitor AA-861 failed to influence the ability of eosinophils to augment the transmembrane flux of albumin. However, insertion of a Millipore filter mask between the eosinophils and the bronchial mucosa significantly inhibited the eosinophil-dependent enhancement of mucosal permeability. 6. The broad spectrum antiproteinase alpha 2-macroglobulin achieved almost total ablation of the action of stimulated eosinophils in the bronchial mucosa. These results suggest that proteinases may make a significant contribution to the genesis of epithelial injury, whereas leukotrienes do not.
Herbert
C A
CA
Immunopharmacology Group, Southampton General Hospital.
Edwards
D
D
Boot
J R
JR
Robinson
C
C
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D046508:Culture Techniques; D003571:Cytochalasin B / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects*; D006168:Guinea Pigs; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D011863:Radioimmunoassay; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
D016227:Benzoquinones; D016859:Lipoxygenase Inhibitors; D012710:Serum Albumin, Bovine; D000001:Calcimycin; D003571:Cytochalasin B; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D004121:Dimethyl Sulfoxide