Abstract
The adult respiratory distress syndrome (ARDS) occurs in patients with various underlying illnesses. It has been suggested that complement activation may play a crucial role in the pathophysiology of ARDS by direct actions of complement fragments and/or by release of mediators including endotoxin, superoxide anion, and arachidonate metabolites.
For clarification of mechanisms for ARDS, we studied functional changes of alveolar macrophages (AM) by using a septic lung model of rats after the operation of cecal ligation and puncture. Septic AM generated significantly less amounts of leukotriene B4 (LTB4), 12- and 5- hydroxyeicosatetraenoic acids (HETEs) by stimulation with A 23187 than the control AM did. Immunoreactive LTC4 in the bronchoalveolar lavage fluids from the septic rats was more than that from the control rats. Therefore, it was speculated that the AM of endotoxemic rats released lipoxygenase metabolites in alveoli and then these AM obtained showed reduced 5-lipoxygenase activity. In contrast, these cells released enhanced amounts of O-2 on stimulation with PMA.
To examine effects of LPS on arachidonate metabolism and O-2 generation, relatively high dose of LPS was i.v administered in rats. The results indicated that AM were activated by the injected LPS to release increased amounts of O-2 and to show enhanced 5-lipoxygenase activity.
It is concluded that such the discrepancy of 5-lipoxygenase activity between AM from LPS-injected rats and those from endogenously endotoxemic rats remains an interesting riddle in the future study of ARDS.
