Contributory role of lung pleura to release of anaphylactic mediators from guinea pig lung in response to ovalbumin or A23187.
Previous findings revealed greater contractile responses of guinea pig lung pleural surface strips to antigen or A23187 challenge than denuded lung parenchymal strips (lung strip devoid of any pleura). Moreover, we have identified a high density of mast cells distributed throughout the lung pleura. The present study examined mediators released from guinea pig lung pleural surface and denuded lung parenchyma fragments in response to immunologic challenge with ovalbumin (OA) or non-immunologic challenge with the ionophore A23187. Histamine levels were measured radioenzymatically; leukotrienes (LTs), prostaglandins (PGs) and thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), were quantitated using an enzyme immunoassay. Histamine release reached a maximal level 3-5 min after OA challenge, whereas A23187-induced histamine release increased gradually in a time-dependent manner. Similar kinetics were observed in the release of LTs, PGs and TXA2. Pleural surface released a substantially (P < 0.05) greater amount of histamine to both challenges than denuded parenchyma. Moreover, histamine content in pleural surface was significantly (P < 0.05) higher than in denuded parenchyma. Pleural surface also released considerably (P < 0.05) more LTB4, LTC4, and LTE4 in response to OA and A23187 than denuded parenchyma. In contrast, pleural surface and denuded parenchyma released equivalent amounts of PGD2, PGE2, PGF2 alpha, and TXA2 in response to both challenges. The rank order of leukotriene release was LTC4 > LTE4 > LTB4, whereas that of prostanoid release was TXA2 >> PGD2 > or = PGF2 alpha >> PGE2. We conclude that pleural surface is the major source of histamine and leukotrienes released from guinea pig lung in vitro in response to OA and A23187, whereas both pleural surface and denuded parenchyma participate to the same extent in prostaglandin and TXA2 production after such challenges.
Wong
W S
WS
Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285.
Spaethe
S M
SM
Henry
D P
DP
Fleisch
J H
JH
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002478:Cells, Cultured; D006168:Guinea Pigs; D006632:Histamine / Q000032:analysis*; D015289:Leukotrienes / Q000032:analysis*; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology*; D010994:Pleura / Q000187:drug effects / Q000276:immunology*; D011453:Prostaglandins / Q000032:analysis; D013931:Thromboxanes / Q000032:analysis
D015289:Leukotrienes; D011453:Prostaglandins; D013931:Thromboxanes; D000001:Calcimycin; D006632:Histamine; D010047:Ovalbumin