In situ localization and regulation of thromboxane A(2) synthase in normal and LPS-primed lungs.
Thromboxane (Tx) A(2) synthase catalyzes the conversion of prostaglandin H(2) to the unstable metabolite TxA(2), which is a potent mediator of vasoconstriction and bronchoconstriction. The cellular localization of TxA(2) synthase was examined by immunohistochemistry and in situ hybridization in human and rat lung tissues. Bronchial epithelial cells, bronchial smooth muscle cells, peribronchial nerve fibers, single cells of bronchus-associated lymphoid tissue, single cells located in the alveolar septum, and alveolar macrophages exhibited positive immunostaining for TxA(2) synthase protein in lung tissue of both species. In addition, vascular smooth muscle cells of muscular and partially muscular vessels displayed strong (rat) and moderate (human) immunostaining for TxA(2) synthase. In situ hybridization performed in the rat lungs demonstrated TxA(2) synthase mRNA localization in accordance with the immunostaining pattern. Perfusing isolated rat lungs with endotoxin for 1 and 2 h resulted in a marked increase in TxA(2) synthase protein staining intensity in most cell types as measured by quantitative image analysis, whereas the in situ hybridization signal was unchanged. We conclude that the pulmonary distribution of TxA(2) synthase displays close similarity between rat and human lung tissues and matches well with the previously described immunolocalization of cyclooxygenase-1 and cyclooxygenase-2 in this tissue. Endotoxin challenge is suggested to cause a rapid upregulation of TxA(2) synthase at the posttranscriptional level. These data provide a morphological basis for the understanding of the role of TxA(2) in the regulation of lung bronchial and vascular tone and in immunologic events.
Ermert
L
L
Department of Pathology, Justus-Liebig-University Giessen, 35385 Giessen, Germany. leander.ermert@anatomie.med.uni-giessen.de
Ermert
M
M
Duncker
H R
HR
Grimminger
F
F
Seeger
W
W
D000818:Animals; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013194:Staining and Labeling; D013930:Thromboxane-A Synthase / Q000378:metabolism*; D014018:Tissue Distribution
D008070:Lipopolysaccharides; D013930:Thromboxane-A Synthase