CONTRIBUTION OF GRANULOCYTOPENIA TO ENDOTOXIN SENSITIVITY OF MICE IRRADIATED OR UNDERGOING GAFT-VERSUS-HOST REACTION

  • 1 January 1976
    • journal article
    • research article
    • Vol. 4  (6) , 329-338
Abstract
Animals compromised by irradiation or graft-vs.-host reaction (GVHR) are highly sensitive to endotoxin (ET). To determine the causes of the increased sensitivity of compromised mice, alterations of hepatic (central) and bloodborne (peripheral) ET clearance processess were studied. Increased sensitivity to ET, as determined by mortality, occurred shortly after irradiation and correlated with granulcytopenia and thrombocytopenia rather than with impairment of liver function. The involvement of granulocytes in ET clearance was indicated by injection of 51Cr-ET suspended in whole blood. By comparison with clearance of ET injected with saline or plasma, greater amounts of 51Cr-Et were sequestered in peripheral organs than in the liver. Similar results were obtained when 51Cr-Et in whole blood was perfused through a rat liver. ET clearance was enhanced 50% over that seen in M-199, plasma or platelet-rich plasma. Intestinal ET contributed to mortality of granulocytopenia-thrombocytopenic mice. This was supported by the observation that bacteriologically decontaminated, irradiated animals were 8 times more resistant to challenge with ET than were conventional animals. Thus, an important aspect of increased sensitivity to ET in comprised mice is defective peripheral clearance.