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Macrophage elimination increases bacterial translocation and gut-origin septicemia but attenuates symptoms and mortality rate in a model of systemic inflammation.

Abstract：

OBJECTIVE:The central question tested in this study was whether dichloromethylene-diphosphonate (CL2MDP) liposome-mediated elimination of hepatic and splenic macrophages would influence zymosan-induced bacterial translocation and the zymosan-induced generalized inflammatory response. SUMMARY BACKGROUND DATA:Both an uncontrolled activation of macrophages and the loss of intestinal barrier function have been implicated in the development of adult respiratory distress syndrome and multiple organ failure. METHODS:Macrophage elimination was accomplished by intravenous injection of 200 microL of CL2MDP-liposome suspension. Control mice received an intravenous injection of 200 microL of phosphate-buffered saline. Two days later, the animals were challenged intraperitoneally with zymosan suspended in paraffin to determine a dose-response curve (0.1, 0.5, or 1.0 mg/g body weight). Twenty-four hours after zymosan challenge, signs of systemic stress were determined, and bacterial translocation to the mesenteric lymph node, liver, spleen, and blood was measured. A separate mortality study was performed with a dose of 1.0 mg/g of zymosan suspension. RESULTS:The incidence of the systemic spread of bacteria was significantly increased in the macrophage-depleted mice. Although systemic bacterial translocation was promoted by macrophage elimination, the systemic toxic response was significantly decreased in all macrophage-depleted groups (p < or = 0.01). The 12-day mortality rate was 0% in the macrophage-depleted groups and 27% in the control group (p = 0.05). CONCLUSIONS:The lethal and toxic effects of zymosan appear to be related more to the excessive activation of macrophages than to the systemic spread of bacteria.

journal_name

Ann Surg

journal_title

Annals of surgery

authors

Nieuwenhuijzen GA,Haskel Y,Lu Q,Berg RD,van Rooijen N,Goris RJ,Deitch EA

doi

10.1097/00000658-199312000-00014

subject

Has Abstract

pub_date

1993-12-01 00:00:00

pages

791-9

issue

eissn

0003-4932

issn

1528-1140

journal_volume

218

pub_type

杂志文章

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Macrophage elimination increases bacterial translocation and gut-origin septicemia but attenuates symptoms and mortality rate in a model of systemic inflammation.