Pharmacologic manipulation of the murine pulmonary biochemical response to NO2

The possible sources of biochemical changes in the lung, including changes in activities of lactate dehydrogenase (LDH), beta-glucuronidase (beta-GLU), choline kinase (CHK), and protease inhibitor (PI), as well as protein content, were evaluated following exposure to NO2. Hydroxyurea-induced granulocytopenia attenuated the LDH and beta-GLU responses (46% and 61%, respectively) following acute, but not subacute, exposure to NO2. Increases in PI activity and pulmonary protein content following exposure to NO2 were not altered by inhibition of protein synthesis by cycloheximide. The observed increase in PI activity appears to result from an activation process, whereas a major source of increased pulmonary protein content following exposure appears to occur from leakage into the lung. The response of the lung to irritant insult is thus dynamic, and the contribution from various sources to the biochemical makeup of the lung following irritant insult may depend on the phase of the pulmonary response.