Differential patterns of apoptosis in resolving and nonresolving bacterialpneumonia

infection with either Streptococcus sanguis or Streptococcus pneumoniae typ e 25 causes acute pneumonitis in rats. Pneumonia caused by S. sanguis resol ves over the course of 8 d, whereas pneumonia caused by S. pneumoniae type 25 progesses to fibrosis. To examine the role of apoptosis in these models, we performed assays with the terminal deoxynucleotidyltransferase-uridine nucleotide end-labeling technique on tissue sections from rat lungs at vari ous times, and quanitified the results with image analysis. Apoptosis was a feature of both the acute and resolving stages of pneumnia. The pattern an d extent of apoptosis were similar in both models during the acute stage, a nd the number of apoptotic nuclei increased in both models through 4 d afte r infection. Although there were differences in the cellular pattern of apo ptosis after 2 d and 4 d of infection, the extent of apoptosis was the same in both models. After 8 d, major differences were observed. In the resolvi ng model, apoptosis was limited primarily to an abscess in the base of the lung. In the nonresolving model, apoptosis was persistent. We also found th at cyclin-dependent kinase-5 expression is upregulated during apoptosis ind uced by bacterial infection. These data indicate that the location and timi ng of apoptosis may determine whether pneumonia resolves or progresses to f ibrosis.