In situ localization and regulation of thromboxane A(2) synthase in normaland 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 vasocons triction and bronchoconstriction. The cellular localization of TxA(2) synth ase 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 lymp hoid tissue, single cells located in the alveolar septum, and alveolar macr ophages exhibited positive immunostaining for TxA(2) synthase protein in lu ng tissue of both species. In addition, vascular smooth muscle cells of mus cular and partially muscular vessels displayed strong (rat) and moderate (h uman) immunostaining for TxA(2) synthase. In situ hybridization performed i n the rat lungs demonstrated TxA(2) synthase mRNA localization in accordanc e with the immunostaining pattern. Perfusing isolated rat lungs with endoto xin 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 ana lysis, whereas the in situ hybridization signal was unchanged. We conclude that the pulmonary distribution of TxA(2) synthase displays close similarit y between rat and human lung tissues and matches well with the previously d escribed immunolocalization of cyclooxygenase-1 and cyclooxygenase-2 in thi s tissue. Endotoxin challenge is suggested to cause a rapid upregulation of TxA(2) synthase at the posttranscriptional level. These data provide a mor phological basis for the understanding of the role of TxA(2) in the regulat ion of lung bronchial and vascular tone and in immunologic events.