Mast cells and resistance to peritoneal sepsis after burn injury.
A mouse model of burn injury demonstrates increasing mortality to an infectious challenge in the form of cecal ligation and puncture (CLP) reaching a peak at 10 days after injury. Because it is widely believed that peritoneal mast cells play an important role in the defense against peritoneal sepsis, we wished to explore the possibility that peritoneal mast cell dysfunction contributed to increased CLP mortality after burn injury. Kit(W-v) C57BL/6 mice, which were shown to lack peritoneal mast cells by cytospin and flow cytometry, and normal littermate control animals were subjected to 25% burn or sham burn injury and 10 days later underwent CLP. Burn injured Kit(W-v) and normal littermates had a high CLP mortality when compared with sham-injured Kit(W-v) and normal littermates (P < 0.003), but the sham- and burn-injured Kit(W-v) and normal littermate animals did not differ from one another with respect to CLP mortality. This result prompted a comparison of CLP mortality in untreated WBB6F1 Kit(W/W-v) mice, known to be mast cell deficient, and normal littermate controls, as well as untreated C57BL/6 Kit(W-v) and normal littermates. The WBB6F1 Kit(W/W-v) mice showed significantly increased mortality after CLP as compared with the littermate controls (P = 0.03), whereas both C57BL/6 Kit(W-v) and littermate controls had very low mortality after CLP. A study of peritoneal cell populations 24 h after CLP failed to reveal an obvious cause for the difference in CLP survival between the two mast cell-deficient strains. Tumor necrosis factor-alpha (TNF-alpha) measurements in peritoneal fluid showed appreciable amounts of TNF-alpha in the littermate controls of both strains and little in the fluid obtained from the mast cell-deficient animals of both strains. We conclude that peritoneal mast cell dysfunction is unlikely to be a major cause of decreased resistance to peritoneal sepsis in burn-injured animals and that the importance of peritoneal mast cells in combating peritoneal sepsis in the mouse appears to be strain dependent.
Shelley
Odhran
O
Department of Surgery, Julian and Eunice Cohen Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Murphy
Thomas
T
Lederer
James A
JA
Mannick
John A
JA
Rodrick
Mary L
ML
D000818:Animals; D002056:Burns / Q000150:complications*; D002432:Cecum / Q000601:surgery; D004195:Disease Models, Animal; D007113:Immunity, Innate; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010532:Peritoneal Diseases / Q000209:etiology / Q000517:prevention & control; D018805:Sepsis / Q000209:etiology / Q000517:prevention & control*; D013154:Spleen / Q000502:physiology / Q000503:physiopathology; D016019:Survival Analysis; D013997:Time Factors