Kazunori Shimoguchi

Potential Activity of Carrageenan to Enhance Antibacterial Host-Defense Systems in Mice

We investigated the influences of carrageenan, generally known to be a selective cytotoxic agent for macrophages, on the antibacterial host-defense systems such as the chemotactic responses to heat-killed bacteria or lipopolysaccharide in the pleural cavity and interleukin-1 production by pleural macrophages. Twenty-four hours after intraperitoneal injection of 200 mg/kg of carrageenan, there were no significant differences in the total and differential cell counts in lavaged fluid from the pleural cavity in carrageenan-pretreated and control mice. After intrapleural injection of heat-killedKlebsiella pneumoniae DT-S or lipopolysaccharide of this strain, significantly greater amounts of leukocytes, predominantly neutrophils, accumulated at 24 hrs in the pleural cavity of carrageenan-pretreated mice compared with control mice (P<0.05). Pleural macrophages obtained from carrageenan-pretreated mice produced more interleukin-1 in response to heat-killedK. pneumoniae DT-S or lipopolysaccharide than the control. Pretreatment with carrageenan significantly prolonged survival of mice against intrapleural challenge withK. pneumoniae DT-S. All 13 control mice died within 48 of inoculation with 9.2×106 organisms per mouse, whereas 11 of 13 carrageenan-pretreated mice survived (P<0.001). These results indicate that carrageenan pretreatment enhances the chemotactic responses to bacterial lipopolysaccharide in the pleural cavity and interleukin-1 production by pleural macrophages. In some experimental conditions, this polysaccharide may act as a macrophage priming agent, instead of macrophage blocker.

Investigations on the Etiology of Sepsis by Using Experimental Mouse Model with Leukocytopenia

Investigation on the etiology of septicemia occurring among the immunocompromised patients was performed by using experimental model of the mouse with leukocytopenia. The ddY conventional mice of 4 weeks of age were inoculated with cyclophosphamide (CPM) intraperitoneally 3 to 5 times every other day with a dose of 3 mg/mouse once to make an agranulocytic status. Then, intraperitoneal administrations of various antibiotic regimens consisting of ampicillin (ABPC) alone, ABPC + ceftazidime (CAZ), ABPC + CAZ + cloxacillin (MCIPC), ABPC + CAZ + MCIPC + minocycline (MINO) and saline as a control to these immunosuppressed mice were begun once every day for 10 days after the second inoculation of CPM. The mortality rate of the mice given saline as a control was very high with a frequency of 43.3% and there were significant differences between the saline group and another antibiotic groups other than ABPC (p less than 0.01). On the other hand, the mortality rate of the group given APBC showed the highest rate of 70% and it was significantly higher than that of the saline control group (p less than 0.05). The main cause of most of the dead mice was septicemia due to P. aeruginosa and which were isolated from the feces of all these mice and serotype of the strains isolated from the heart blood and feces in the same host corresponded to each other. Moreover, intestinal bacterial flora in mice treated by saline and ABPC which highly showed Pseudomonas sepsis, was occupied dominantly by P. aeruginosa, although P. aeruginosa was not detectable from the experimental environments.(ABSTRACT TRUNCATED AT 250 WORDS)