Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 2043-2050

Differential Patterns of Apoptosis in Resolving and Nonresolving Bacterial Pneumonia

JEFFREY A. KAZZAZ, STUART HOROWITZ, JING XU, POONAM KHULLAR, MICHAEL S. NIEDERMAN, ALAN M. FEIN, ZAHRA ZAKERI, LIN LIN, and GREGORY C. RHODES

CardioPulmonary Research Institute and Departments of Pathology and Medicine, Winthrop-University Hospital, Mineola; Department of Medicine, North Shore University Hospital, Manhasset; and Department of Biology, Queen's College, New York, New York; and Orange Regional Laboratory, Orange, Australia

Infection with either Streptococcus sanguis or Streptococcus pneumoniae type 25 causes acute pneumonitis in rats. Pneumonia caused by S. sanguis resolves 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 various times, and quanitified the results with image analysis. Apoptosis was a feature of both the acute and resolving stages of pneumnia. The pattern and extent of apoptosis were similar in both models during the acute stage, and the number of apoptotic nuclei increased in both models through 4 d after infection. Although there were differences in the cellular pattern of apoptosis 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 resolving model, apoptosis was limited primarily to an abscess in the base of the lung. In the nonresolving model, apoptosis was persistent. We also found that cyclin-dependent kinase-5 expression is upregulated during apoptosis induced by bacterial infection. These data indicate that the location and timing of apoptosis may determine whether pneumonia resolves or progresses to fibrosis.

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