scholarly journals Uptake and intracellular activity of NM394, a new quinolone, in human polymorphonuclear leukocytes.

1996 ◽  
Vol 40 (3) ◽  
pp. 739-742 ◽  
Author(s):  
M Ozaki ◽  
K Komori ◽  
M Matsuda ◽  
R Yamaguchi ◽  
T Honmura ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infection ◽  
Polymorphonuclear Leukocytes ◽  
Concentration Ratio ◽  
Extracellular Concentration ◽  
Intracellular Activity ◽  
Subsequent Elution ◽  
Active Transport System ◽  
Human Polymorphonuclear Leukocytes ◽  
Kinetics Of

The uptake of NM394, a new quinolone, by and its subsequent elution from human polymorphonuclear leukocytes were studied and compared with those of ofloxacin and ciprofloxacin. The kinetics of the uptake of NM394 was similar to that of ciprofloxacin. The maximum intracellular-to-extracellular concentration ratio was 12.3, compared with 8.6 for ciprofloxacin and 4.9 for ofloxacin at the extracellular concentration of 20 micrograms/ml. The elution of NM394 from human polymorphonuclear leukocytes occurs relatively slowly; 5 min after the removal of extracellular NM394, nearly 100% still remained in polymorphonuclear leukocytes, compared with ofloxacin, which was so rapidly eluted that only 12% remained. The uptake of NM394 was significantly decreased at 4 degrees C and by the presence of NaCN but was not affected by the presence of L-glycine, L-leucine, L-serine, adenosine, or NaF. NM394 showed intracellular activity at a concentration of 0.1 microgram/ml that significantly reduced the number of phagocytosed Pseudomonas aeruginosa cells with 2 h of incubation. These results suggest that uptake of NM394 by human polymorphonuclear leukocytes occurs via an active transport system differing from that of ofloxacin, whose uptake is affected by the presence of L-glycine and L-leucine, and that once accumulated, NM394 remains intracellularly active and participates in protection against bacterial infection.

scholarly journals Uptake and intracellular activity of trovafloxacin in human phagocytes and tissue-cultured epithelial cells.

1997 ◽  
Vol 41 (2) ◽  
pp. 274-277 ◽  
Author(s):  
A Pascual ◽  
I García ◽  
S Ballesta ◽  
E J Perea
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Polymorphonuclear Leukocytes ◽  
Peritoneal Macrophages ◽  
Extracellular Concentration ◽  
Opsonized Zymosan ◽  
Intracellular Activity ◽  
Cultured Epithelial Cells ◽  
Energy Dependent ◽  
Human Polymorphonuclear Leukocytes

The penetration of trovafloxacin into human polymorphonuclear leukocytes (PMNs), human peritoneal macrophages, and tissue-cultured epithelial cells (McCoy cells) was evaluated. The cellular concentration to extracellular concentration (C/E) ratios of trovafloxacin were greater than 9 for extracellular concentrations ranging from 0.5 to 25 micrograms/ml. The uptake of trovafloxacin by PMNs was rapid, reversible, nonsaturable, not energy dependent, and significantly increased at 4 degrees C. Ingestion of opsonized zymosan, but not opsonized Staphylococcus aureus, significantly increased the amount of PMN-associated trovafloxacin. This agent at concentrations of 0.5 and 1 microgram/ml induced a greater reduction in the survival of intracellular S. aureus in PMNs than ciprofloxacin and ofloxacin. It was concluded that trovafloxacin reaches concentrations within phagocytic and nonphagocytic cells several times higher than the extracellular ones, while it remains active in PMNs.

scholarly journals Thymosin beta 4 sequesters the majority of G-actin in resting human polymorphonuclear leukocytes.

1992 ◽  
Vol 119 (5) ◽  
pp. 1261-1270 ◽  
Author(s):  
L Cassimeris ◽  
D Safer ◽  
V T Nachmias ◽  
S H Zigmond
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Actin Polymerization ◽  
Large Fraction ◽  
Reverse Phase Hplc ◽  
Thymosin Beta 4 ◽  
Rapid Changes ◽  
Human Pmns ◽  
Human Polymorphonuclear Leukocytes ◽  
Kinetics Of

Thymosin beta 4 (T beta 4), a 5-kD peptide which binds G-actin and inhibits its polymerization (Safer, D., M. Elzinga, and V. T. Nachmias. 1991. J. Biol. Chem. 266:4029-4032), appears to be the major G-actin sequestering protein in human PMNs. In support of a previous study by Hannappel, E., and M. Van Kampen (1987. J. Chromatography. 397:279-285), we find that T beta 4 is an abundant peptide in these cells. By reverse phase HPLC of perchloric acid supernatants, human PMNs contain approximately 169 fg/cell +/- 90 fg/cell (SD), corresponding to a cytoplasmic concentration of approximately 149 +/- 80.5 microM. On non-denaturing polyacrylamide gels, a large fraction of G-actin in supernatants prepared from resting PMNs has a mobility similar to the G-actin/T beta 4 complex. Chemoattractant stimulation of PMNs results in a decrease in this G-actin/T beta 4 complex. To determine whether chemoattractant induced actin polymerization results from an inactivation of T beta 4, the G-actin sequestering activity of supernatants prepared from resting and chemoattractant stimulated cells was measured by comparing the rates of pyrenyl-actin polymerization from filament pointed ends. Pyrenyl actin polymerization was inhibited to a greater extent in supernatants from stimulated cells and these results are qualitatively consistent with T beta 4 being released as G-actin polymerizes, with no chemoattractant-induced change in its affinity for G-actin. The kinetics of bovine spleen T beta 4 binding to muscle pyrenyl G-actin are sufficiently rapid to accommodate the rapid changes in actin polymerization and depolymerization observed in vivo in response to chemoattractant addition and removal.

scholarly journals Uptake and intracellular activity of AM-1155 in phagocytic cells.

1996 ◽  
Vol 40 (12) ◽  
pp. 2756-2759 ◽  
Author(s):  
T Yamamoto ◽  
H Kusajima ◽  
M Hosaka ◽  
H Fukuda ◽  
Y Oomori ◽  
...  
Keyword(s):  
Cell Types ◽  
Intracellular Concentration ◽  
Nucleoside Transport ◽  
Metabolic Inhibitors ◽  
Phagocytic Cells ◽  
Penetration Process ◽  
Extracellular Concentration ◽  
Intracellular Activity ◽  
Human Polymorphonuclear Leukocytes

The uptake and intracellular activity of AM-1155 in murine J774.1 macrophages and human polymorphonuclear leukocytes were investigated. AM-1155 penetrated phagocytic cells rapidly and reversibly, although the penetration process was not affected by metabolic inhibitors such as sodium fluoride, cyanide m-chlorophenylhydrazone, or ouabain or by nucleoside transport system inhibitors such as adenosine. The intracellular concentration-to-extracellular concentration ratio of AM-1155 in both cell types of phagocytes ranged from 5 to 7. These ratios were almost equal to those for sparfloxacin. The intracellular activity of AM-1155 in J774.1 macrophages, examined with Staphylococcus aureus 209P as a test bacterium, was dependent on the extracellular concentration. AM-1155 at a concentration of 1 microgram/ml reduced the number of viable cells of S. aureus ingested by more than 90%. The intracellular activity of AM-1155 was more potent than those of sparfloxacin, ofloxacin, ciprofloxacin, flomoxef, and erythromycin. These results suggest that the potent intracellular activity of AM-1155 might mainly be due to the high intracellular concentration and its potent in vitro activity.

scholarly journals Uptake and Intracellular Activity of Linezolid in Human Phagocytes and Nonphagocytic Cells

2002 ◽  
Vol 46 (12) ◽  
pp. 4013-4015 ◽  
Author(s):  
Álvaro Pascual ◽  
Sofía Ballesta ◽  
Isabel García ◽  
Evelio J. Perea
Keyword(s):  
Cell Viability ◽  
Staphylococcus Epidermidis ◽  
Polymorphonuclear Leukocytes ◽  
Environmental Temperature ◽  
Cultured Cells ◽  
Intracellular Activity ◽  
Intracellular Concentrations ◽  
Human Polymorphonuclear Leukocytes

ABSTRACT The intracellular penetration and activity of linezolid in human polymorphonuclear leukocytes and tissue-cultured cells (McCoy) were evaluated. Linezolid reached intracellular concentrations slightly greater than extracellular ones in both types of cell. The uptake was rapid and not saturable and was affected by environmental temperature and cell viability. Linezolid showed slight intracellular activity against Staphylococcus epidermidis at high extracellular concentrations.

scholarly journals The effect of Pseudomonas aeruginosa cytotoxin and toxin A on human polymorphonuclear leukocytes

1987 ◽  
Vol 24 (4) ◽  
pp. 315-324 ◽  
Author(s):  
M. B. Bishop ◽  
A. L. Baltch ◽  
L. A. Hill ◽  
R. P. Smith ◽  
F. Lutz ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Polymorphonuclear Leukocytes ◽  
Toxin A ◽  
Human Polymorphonuclear Leukocytes

scholarly journals Antipseudomonal Agents Exhibit Differential Pharmacodynamic Interactions with Human Polymorphonuclear Leukocytes against Established Biofilms of Pseudomonas aeruginosa

2015 ◽  
Vol 59 (4) ◽  
pp. 2198-2205 ◽  
Author(s):  
Athanasios Chatzimoschou ◽  
Maria Simitsopoulou ◽  
Charalampos Antachopoulos ◽  
Thomas J. Walsh ◽  
Emmanuel Roilides
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Respiratory Tract ◽  
Polymorphonuclear Leukocytes ◽  
Planktonic Cells ◽  
Phagocytic Cells ◽  
Positive Interaction ◽  
Content Type ◽  
Pharmacodynamic Interactions ◽  
Human Pmns ◽  
Human Polymorphonuclear Leukocytes

ABSTRACTPseudomonas aeruginosais the most common pathogen infecting the lower respiratory tract of cystic fibrosis (CF) patients, where it forms tracheobronchial biofilms.Pseudomonasbiofilms are refractory to antibacterials and to phagocytic cells with innate immunity, leading to refractory infection. Little is known about the interaction between antipseudomonal agents and phagocytic cells in eradication ofP. aeruginosabiofilms. Herein, we investigated the capacity of three antipseudomonal agents, amikacin (AMK), ceftazidime (CAZ), and ciprofloxacin (CIP), to interact with human polymorphonuclear leukocytes (PMNs) against biofilms and planktonic cells ofP. aeruginosaisolates recovered from sputa of CF patients. Three of the isolates were resistant and three were susceptible to each of these antibiotics. The concentrations studied (2, 8, and 32 mg/liter) were subinhibitory for biofilms of resistant isolates, whereas for biofilms of susceptible isolates, they ranged between sub-MIC and 2 × MIC values. The activity of each antibiotic alone or in combination with human PMNs against 48-h mature biofilms or planktonic cells was determined by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. All combinations of AMK with PMNs resulted in synergistic or additive effects against planktonic cells and biofilms ofP. aeruginosaisolates compared to each component alone. More than 75% of CAZ combinations exhibited additive interactions against biofilms ofP. aeruginosaisolates, whereas CIP had mostly antagonistic interaction or no interaction with PMNs against biofilms ofP. aeruginosa. Our findings demonstrate a greater positive interaction between AMK with PMNs than that observed for CAZ and especially CIP against isolates ofP. aeruginosafrom the respiratory tract of CF patients.

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