Histologic, cytologic, and bacteriologic examinations of experimentally induced Salmonella typhimurium infection in Lewis rats.
OBJECTIVE
Histopathologic changes, cellular composition, and bacterial spreading were studied in rat spleen after experimentally induced infection with Salmonella typhimurium.


METHODS
Lewis rats were inoculated intraperitoneally with 10(6) bacteria. Spleen weight, cell numbers, and cell surface markers were studied together with histopathologic changes, and expression of inducible nitric oxide synthase (iNOS). The spread of bacteria to blood, spleen, liver, mesenteric lymph nodes, lung, and kidney was studied at 12 hours, and 1, 3, 7, 14, and 28 days after inoculation.


RESULTS
Experimentally induced infection caused an increase in spleen weight and leukocyte numbers, and a decrease in CD49d, on postinoculation days (PID) 3 through 7. Numerous granulomas were disseminated throughout the splenic red pulp also on PID 3 through 7. From PID 14 on, clearance of cellular exudate and regeneration of tissue structure were observed. Massive expression of iNOS was seen on PID 3. Bacterial growth was observed in liver and spleen from 12 hours to 14 days after inoculation. Bacteria were detected in blood on PID 3 and mesenteric lymph nodes were infected from PID 3 through 14.


CONCLUSIONS
Salmonella typhimurium was rapidly taken up by the reticuloendothelial system. The infection induced weight increase and reversible changes in the spleen, peaking on PID 3 with granuloma formation and infiltration with macrophages. On PID 3, extensive production of iNOS within the granulomas was observed, suggesting initial killing of phagocytosed bacteria, followed by bacterial clearance and tissue regeneration. Cell surface marker expression on CD4+ T cells indicated no change in their numbers; however, there was a time-dependent change in expression of CD49d.
Thygesen
P
P
Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen.
Martinsen
C
C
Hougen
H P
HP
Hattori
R
R
Stenvang
J P
JP
Rygaard
J
J
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000382:microbiology / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009929:Organ Size; D051381:Rats; D011917:Rats, Inbred Lew; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D012486:Salmonella typhimurium / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D013154:Spleen / Q000201:enzymology / Q000382:microbiology / Q000473:pathology
D000954:Antigens, Surface; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat