Microbiology and immunology
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Microbiol. Immunol. · Jan 1998
Anti-Candida activity of calprotectin in combination with neutrophils or lactoferrin.
The effect of an anti-microbial protein, calprotectin, in combination with neutrophils on the growth of Candida albicans was investigated. The growth inhibition of C. albicans by murine neutrophils was augmented by the addition of a low concentration of calprotectin prepared from rat peritoneal exudate cells. ⋯ Lactoferrin, which is an anti-microbial protein released from neutrophils, strongly inhibited the growth of C. albicans in combination with calprotectin. These results suggest that calprotectin and lactoferrin released from neutrophils may cooperate to inhibit the growth of C. albicans at a local lesion of the infection where there is an accumulation of neutrophils.
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Microbiol. Immunol. · Jan 1998
Kinetical analysis of tumor cell death-inducing mechanism by polymorphonuclear leukocyte-derived calprotectin: involvement of protein synthesis and generation of reactive oxygen species in target cells.
We have previously shown that calprotectin, the most abundant cytosolic protein existing in polymorphonuclear leukocytes (PMNs), induces apoptotic cell death in various tumor cells, suggesting that calprotectin is an effector molecule against tumor cells in PMNs. To explore the cell death-inducing mechanism of the factor, we examined the involvement of target protein synthesis and generation of reactive oxygen species (ROS) in the reaction. Calprotectin induced cell death in MM46 mouse mammary carcinoma cells after a 14-16 hr lag time. ⋯ The addition of NAC even 15 hr later significantly attenuated the calprotectin effect. Flow cytometry analysis showed that calprotectin began to increase the ROS content in MM46 cells after 8-12 hr of culturing, and that the increase was abrogated by the antioxidants. Thus, protein synthesis and ROS generation may be essential elements in the early or later phases of the cell death-inducing reaction of calprotectin, respectively.
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Microbiol. Immunol. · Jan 1997
Endogenous tumor necrosis factor (TNF) alpha mediates neutrophil accumulation at the mid-phase of a murine model of Pseudomonas aeruginosa pneumonia.
To determine the role of endogenous tumor necrosis factor (TNF) alpha on neutrophil influx into the lungs in acute Pseudomonas aeruginosa pneumonia, we evaluated TNF alpha activity, inflammatory cell response and neutrophil chemotactic activity in the bronchoalveolar lavage fluids (BALFs) of P. aeruginosa-infected mice. In the case of fatal pneumonia, the TNF alpha activity in the BALFs appeared within 3 hr, peaked at 6-12 hr and attenuated within 24 hr after intratracheal challenging, while no TNF alpha activity was detected in the plasma. The elevation of TNF alpha activity in the BALFs was closely associated with neutrophil accumulation. ⋯ Neutralization of the TNF alpha activity in the BALFs with anti-murine TNF antiserum decreased the level of neutrophil migration by BALF 45.0-49.7% at 6 hr and 49.3-54.2% at 12 hr, while the neutralizing antiserum had no effect on the level of neutrophil migration by BALFs at 3 and 24 hr. Furthermore, the intravenous administration of anti-murine TNF antiserum 2 hr before challenging significantly inhibited neutrophil migration into the lungs of mice with sublethal pneumonia (P < 0.05; compared with mice receiving pre-immune serum). These data suggest that intra-alveolar TNF alpha plays an important role in causing lung neutrophil accumulation at the mid-phase of murine P. aeruginosa pneumonia.
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Microbiol. Immunol. · Jan 1994
Comparative StudyComparison of the virulence of methicillin-resistant and methicillin-sensitive Staphylococcus aureus.
The virulence of methicillin-resistant Staphylococcus aureus (MRSA) was compared with that of methicillin-sensitive S. aureus (MSSA), using 13 MRSA and 7 MSSA strains isolated from clinical specimens. The infectivity and lethality of the two groups were examined as to the inoculum required to infect 50% of guinea pigs (ID50) and to kill 50% of mice (LD50), respectively. The mean ID50 [log10 colony forming units (CFU)] for MRSA strains was 7.1 +/- 0.60 standard deviation, which was 1.5 higher than that for MSSA strains (P < 0.001). ⋯ Pretreatment of mice with cyclophosphamide decreased the mean LD50 for MRSA strains more than that for MSSA strains, resulting in the difference in the mean LD50 being insignificant (P = 0.502). These results indicate that MRSA is less virulent than MSSA in normal hosts, but that they are equally virulent in immunocompromised hosts. The growth of MRSA strains was much slower than that of MSSA strains in the lag phase, although their growth rates were almost the same in the exponential growth phase, suggesting that the difference in virulence between them may be at least partly due to such a difference in growth.
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Microbiol. Immunol. · Jan 1991
Pharmacodynamic and protective properties of a murine lipopolysaccharide-specific monoclonal antibody in experimental Pseudomonas aeruginosa pneumonia in mice.
We employed a Pseudomonas aeruginosa mouse pneumonia model to evaluate the ability of a murine monoclonal antibody (MAb) specific for the O-side chain of P. aeruginosa Fisher Immunotype-1 lipopolysaccharide (LPS) to achieve and sustain therapeutic levels in plasma and lung tissue, reduce bacterial populations in the lung, and prevent pneumonia-associated mortality. An IgG3 MAb (Y1-5A4) administered to mice i.v. over a dose range of 125-1,000 micrograms/mouse produced plasma and lung tissue levels at 2 hr of 61-507 micrograms/ml and 4.3-150 micrograms/g, respectively. The 1,000 micrograms MAb dose reduced bacterial counts in lung tissue (log10 cfu/g +/- S. ⋯ Protection was noted following administration of 1,000 micrograms of MAb up to 6 hr after bacterial challenge (P less than 0.05, compared with untreated control). Histological examination of lung tissue from infected mice revealed less acute inflammation, necrosis, and hemorrhage in MAb-treated compared with untreated control animals and greater localization of Pseudomonas antigen within the phagocytic cells in alveolar space. These findings document the in vivo therapeutic efficacy of an LPS-specific IgG MAb in a murine model of acute P. aeruginosa pneumonia, based in part upon the achievability of effective MAb concentrations in plasma and lung tissue.