Key words: bacteremia, reticuloendothelial system, bacterial clearance, Kupffer cell, bacterial phagocytosis Pseudomonas aeruginosa (P. aeruginosa) Mo
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1 Key words: bacteremia, reticuloendothelial system, bacterial clearance, Kupffer cell, bacterial phagocytosis Pseudomonas aeruginosa (P. aeruginosa) Morganella morganii (M. morganii) Escherichia coli (E. coli) En to ro bacter cloacae (E. cloacae)
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3 Table 1 Bacterial species and number of strains isolated from experimental bacteremic mice A. conventional mice (n=30) B. SPF mice (n=133) a) isolated from both the heart blood and the liver or the portal vein blood b) isolated from only the liver, not isolated from the heart blood c) isolated from only the portal vein blood, not iso- from the heart blood lated ( ): Number of mixed isolates The incidence of bacteremia involving portal bacter- in conventional mice was statistically emia significantly higher than in SPF mice (p<0.01).
4 Fig. 1 Blood clearance of isolated bacteria in mice The results are expressed as the mean recovery percentages } the standard deviation (SD) (n= 5). The time zero values were calculated by estimating the total blood volume as 8% (vol/wt) of the mice used. The clearance rates of both of M. morganii and P. aeruginosa were statistically K. pneumoniae at all measuring time (p < 0.01). M. morganii significantly lower than of E. coli, E. cloacae and P. aeruginosa K. pneumoniae minutes afterinoculation E. cloacae
5 Fig. 2 Effect of cyclophosphamide and/or carrageenan on blood clearance of K. pneumoniae The results are expressed as the mean recovery percentages }SD (n=3). o: control, œ: treated with 3mg of cyclophosphamide 6, 4, ldays before, A: treated with 4mg of carrageenan 24hr before, o: treated with cyclophosphamide and carrageenan according to the above. Fig. 3 Effect of BCG on blood clearance of P. aeruginosa and M. morganii The results are expressed as the mean recovery percentages } SD (n=5). o: treated with 0.2ml of saline intraperitoneally 2ldays before, œ: treated with 1.0mg of BCG in 0.2m1 of saline according to above The clearance rates of both bacteria in mice treated with BCG were statistically significantly higher than in mice treated with only saline. P. aeruginosa p<0.01 at all measuring time. M. morganii ; p< 0.05 at 5, 10, 15min and p <0.01 at 30min.
6 Fig. 4 Effect of antiserum on blood clearance of P. aeruginosa and M. morganii The results are expressed as the mean recovery percentages SD (n=5). o: treated with 0.2m1 of the normal serum (10% in saline) intravenously 30 min before, œ: treated with 0.2m1 of the antiserum according to the above The clearance rates of both bacteria in mice treated with the antiserum were statistically significantly higher than in mice treated with the normal serum at all measuring time (p <0.01). P. aeruginosa M. morganii Fig. 5 Sensitivity of bacteria to normal serum The results are expressed as the recovery per centage at 30 min after inoculation compared with the initial number of bacteria. P. aeruginosa M. morganii E. coli K. pneumoniae E. cloacae
7 Table 2 Distribution of bacteria in mice at 30 min after inoculation intravenously A. % of viable bacteria in blood and organ B. ratio of bacteria in organ (CFU/g) /bacteria in blood (CFU/ml) A.: The results are expressed as the mean recovery percentage SD(n=3). B.: Each data are calculated by using the mean number of A. Fig. 6 Clearance of bacteria by perfused livers of E. coli and P. aeruginosa The results are expressed as the mean recovery percentage (n=3). The clearance rate of E. coli by perfused livers was statistically significantly higher than of P. aeruginosa (p< 0.01). E. coti P. aeruginosa
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9 2) Schimpff, S. C., Young, V. M., Greene, W. H., Vermeulen, G. D., et al.: Origin of infection in acute nonlymphocytic leukemia-significance of hospital acquisition of potential pathogens. Ann. Intern. Med., 77: , 1972.
10 3) Ueda, T., Shibata, H., Nakamura, H., Takubo, T., et al.: Efficacy of laminar air flow room with or without clean nursing for preventing infection in patients with acute leukemia. Jpn. J. Clin. Oncol., 13 (Suppl): , reference to encapsulated bacteria. Bact. Rev., 24: 41-49, ) Stuart, A. E.: The reticuloendothelial system. 5) Young, L. S., Stevens, P. & Kaijser, B.: Gramnegative pathogens in septicaemic infections. The mechanisms by which macrophages Scand. J. Infect. Dis., 31(Suppl): 78-94, phagocyte encapsulated bacteria in the absence of antibody. J. Exptal. Med., 100: , ) Brown, E. J., Hosea, S. W. & Frank, M. M.: The role of complement in the localization of pneumococci in the splanchnic reticuloendoth- system during experimental bacteremia. J. elial Immun., 126: , ) Leunk, R. D. & Moon, R. J.: Association of 17) Horwitz, M. A.: Serial feature-phagocytosis type 1 pili with the ability of livers to clear of microorganisms. Rev. Infect. Dis., 4: 104 Salmonella typhimurium. Infect. Immun., 36: 123, , ) McCuskey, R. S., McCuskey, P. A., Urbaschek, 9) Biozzi, G. & Stiffel, C.: The physiopathology R. & Urbaschek, B.: Species differences in of the reticuloendothelial cells of the liver and Kupffer cells and endotoxin sensitivity. Infect. spleen. In Progress in liver disease, Vol. II Immun., 45: , (Popper, H. and Schaffener, F. ed. ) p , 19) Peavy, D. L., Baughn, R. E. & Musher, D. M.: William Heinemann Medical Books, London, Effects of BCG infection on the susceptibility of mouse macrophages to endotoxin. Infect. Immun., 24: 59-64, ) Altura, B. M.: Reticuloendothelial cells and host defense. Adv. Microcirc., 9: , ) Dalen, D. P. P., Brouwer, A. & Knook, D. L.: Clearance capacity of rat liver Kupffer, endothelial and parenchymal 81: , cells. Gastroenterology, 13) Wood, W. B.: Phagocytosis, with particular p E. & S. Livingstone, London, ) Sawyer, W. D., Smith, M. R. & Wood, W. B.:
11 Investigations on Etiology of Sepsis by Using Experimental Mouse Model with Leukocytopenia 2. The Role of the Reticuloendothelial System in the Etiology of Bacteremia Yohichi HIRAKATA1), Keizo YAMAGUCHI1), Kazunori TOMON01), Kazunori SHIMOGUCHI1), Kazuhiro TATEDA1}, Kazuo NOUDA1), Kazuyuki SUGAHARAI), Shigeru KOHNO2), Masaki HIROTA2) & Kohei HARA2) 1) Department of Laboratory Medicine, Nagasaki University School of Medicine 2) Second Department of Internal Medicine, Nagasaki University School of Medicine It has been recognized by clinical data that most of sepsis occurring in the immunocompromised host are endogenous infection. In recent years, we have investigated the mechanism of these bacteremia and sepsis by experimental studies using neutropenic mice treated with cyclophosphamide. And we evidenced that most pathogens causing bacteremia originated in the intestinal flora of the host. It has been shown that bacteria causing bacteremia were divided into two main groups, causing systemic bacteremia and causing portal bacteremia. Pseudomonas aeruginosa and Morganella morganii belonged to the former, on the other hand, Escherichia coli, Enterobacter cloacae and some other bacteria belonged to the latter. In this study, we studied the role of the reticuloendothelial system (RES) in the etiology of bacteremia or sepsis, using various kinds of bacteria isolated from bacteremic mice. As a result, the following facts were revealed. 1. It was suggested that the low blood clearance rate of the bacteria was one of the great risk factor of systemic bacteremia, since the blood clearance rate of bacteria causing systemic bacteremia was significantly lower than those of bacteria causing portal bacteremia. 2. Bacteria in the blood were eliminated by the RES, mainly by the liver, and the level of bacterial clearance by the liver was relative to the type of bacteremia which was systemic or portal. 3. It was suggested that the bacterial clearnace by the liver mainly reflected the phagocytosis by Kupffer cells, and especially the adherence of these cells to bacteria as the first step of phagocytosis.
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