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R Dziarski

Publications and source records attributed to R Dziarski.

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Synergistic enhancement of T cell responses and interleukin-1 receptor expression by interleukin-1 and heparin or dextran sulfate.

Heparin markedly enhances generation of cytotoxic T lymphocytes against allogeneic cells and histocompatible tumors. In this study, we demonstrated a marked synergism between heparin and low concentrations of recombinant IL-1-alpha and IL-1-beta in enhancement of cytotoxic T cell responses in mice. Low molecular weight (8000 Da) dextran sulfate also enhanced the T cell responses and synergized with IL-1, whereas, de-N-sulfated heparin was devoid of both of these activities. The synergistic effect was selective for IL-1, because there was no synergism between heparin or dextran sulfate and other cytokines (tumor necrosis factor-alpha, IL-4, and, as shown previously, IL-2). Heparin did not increase the production of IL-1 (and IL-2, as shown before). Heparin did not bind to IL-1, despite significant amino acid homology between IL-1 and heparin-binding endothelial cell growth factors. Heparin enhanced the growth-promoting effect of IL-1 on the IL-1-dependent helper T cell clone, D10.G4.1, and enhanced IL-1 receptor expression on these cells. These data indicate that heparin acts directly on the T cells and enhances their responsiveness to IL-1 by up-regulating IL-1 receptor expression.

Animals

Mitogenic activity of staphylococcal peptidoglycan.

Staphylococcus aureus peptidoglycan displayed a marked dose-dependent mitogenic activity for mouse splenocytes and human peripheral blood lymphocytes in vitro, as measured by increased [3H]thymidine incorporation. Similarly it was mitogenic for athymic nude mouse spleen cells, whereas no blastogenic effect was observed in T cell-enriched and B cell-depleted mouse lymphocyte cultures. These data demonstrate that peptidoglycan-responding cells in mouse spleen cell cultures are B lymphocytes.

Animals

Relationships between adjuvant, immunosuppressive, and mitogenic activities of staphylococcal peptidoglycan.

Staphylococcal peptidoglycan (PG) possesses in vivo immunodulating activity and is a B-cell mitogen in mice. The effect of PG on in vitro immune response of mouse splenocytes to sheep erythrocytes (SRBC) was studied, as well as the relationships between in vivo and in vitro adjuvant, immunosuppressive, and mitogenic activities of PG in terms of dose response, time kinetics, and physical state. Particulate PG suppressed in vivo anti-SRBC response when injected in a large dose before or simultaneously with SRBC. A small dose of particulate PG given before or along with the antigen was immunostimulatory. Soluble PG was adjuvant active in both high and low doses when injected before or along with the antigen. Both PG preparations were adjuvant active for mouse splenocytes in vitro immunized with SRBC, but particulate PG was more active. Even high doses of particulate PG were not directly suppressive for the in vitro immune response. Particulate PG was also mitogenic for mouse splenocytes, and the maximum increase in [3H]thymidine incorporation was observed after 2 days of culture. Soluble PG was not mitogenic during the 5-day incubation period. These results indicate that the physical state of PG, its dose, and its time of application are important factors determining its immunomodulating and mitogenic activities, and that by changing them it is possible to dissociate the adjuvant, immunosuppressive, and mitogenic properties of PG.

Adjuvants, Immunologic

Immunosuppressive effect of Staphylococcus aureus peptidoglycan on antibody response in mice.

Immunosuppressive effect of an adjuvant, Staphylococcus aureus peptidoglycan, on the primary IgM antibody response in mice was studied with application of the hemolytic plaque assay. Peptidoglycan suppressed the IgM response to thymus-dependent sheep erythrocyte antigen when given intravenously before immunization. The effect of peptidoglycan and erythrocytes was both time and dose dependent. For the suppression, both the delay in the antibody response and overall decreased response were responsible. Peptidoglycan did not influence background counts of antibody-forming cells. Priming with subthreshold dose of erythrocytes did not overcome the suppression, although higher responses compared to unprimed animals were observed. Peptidoglycan did not suppress antibody response to thymus-independent antigens-lipopolysaccharide or high dose of erythrocytes. It is suggested that peptidoglycan-induced immunosuppression is mediated by a presently unidentified population of helper cells-macrophages or T lymphocytes.

Animals

Delayed type hypersensitivity to Staphylococcus aureus peptidoglycan in guinea pigs.

Skin hypersensitivity to Staphylococcus aureus peptidoglycan in guinea pigs was studied. For distinct skin reaction injection of 50 microgram of the antigen was required. Nonsensitized guinea pigs and animals sensitized with emulsion of 1 mg or 100 microgram of peptidoglycan with complete or incomplete FREUND's adjuvant exhibited distinct immediate skin hypersensitivity. Nonsensitized animals did not show delayed type hypersensitivity (DTH). For development of DTH sensitization with 100 microgram of the antigen with incomplete FREUND's adjuvant was sufficient. The application of complete FREUND's adjuvant resulted in intensification of DTH; however, also nonspecific sensitization to staphylococcal peptidoglycan with Mycobacterium butyricum cells, present in complete adjuvant, occurred.

Animals

Stimulation of reticuloendothelial system and toxicity to macrophages of Staphylococcus aureus cell wall, peptidoglycan, and teichoic acid.

Staphylococcus aureus cell wall possesses several biological activities. It is removed from the blood by reticuloendothelial system (RES) and persists there for a long time. The influence of cell wall components on RES cells in vivo and in vitro was investigated. RES activity was studied in mice by carbon clearance method. Intravenous injection of 10 microgram of cell walls or peptidoglycan caused early stimulation and subsequent suppression of RES activity, while teichoic acid was inactive. Four hundred microgram of peptidoglycan caused RES stimulation with maximum after three days, whereas 400 microgram of cell walls caused no such stimulation. Viability of mouse peritoneal macrophages was studied after four days of culture in the presence of cell walls, peptidoglycan, and teichoic acid. Fifty microgram/ml of cell walls or peptidoglycan caused death of all or 68% of macrophages respectively. Teichoic acid was inactive, exhibiting toxic effects at 400 microgram/ml level.

Animals

Teichoic acids.

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Animals

Susceptibility of Staphylococcus aureus, Streptococcus pyogenes and Diplococcus pneumoniae to antibiotics. Comparison of patterns in Poland and Federal Republic of Germany.

One hundred and eighty five strains of Gram-positive cocci were tested for susceptibility to 16 antibiotics, including some newer drugs, by agar dilution technique. Of these, 100 strains (50 each isolated in Poland and Germany) were Staphylococcus aureus, 55 Streptococcus pyogenes, and 30 Diplococcus pneumoniae. Previous investigations of streptococci and pneumococci isolated in Poland and Federal Republic of Grmany, revealed no differences in antibiotic-susceptibility patterns in both countries, which was not the case with staphylococci. Present study demonstrates further evidence for existence of differences in antibiotic-sensitivity of staphylococci, depending of their geographical origin, and presents actual state of susceptibility to antibiotics of Streptococcus pyogenes and Diplococcus pneumoniae.

Anti-Bacterial Agents

Susceptibility of Streptococcus faecalis to 32 antimicrobial agents. Comparison of patterns in Poland and Federal Republic of Germany.

Two hundred and twenty strains of Streptococcus faecalis (103 isolated in Poland and 117 in Federal Republic of Germany), were tested for antibiotic-susceptibility to 32 antimicrobial agents by agar dilution technique. Most effective in vitro appeared ampicillin, penicillin G, and a combination (1:1) of penicillin and streptomycin. Partly effective were also macrolide antibiotics, trimethoprim + sulfamethoxazole and five tetracyclines. Other antibiotics, including five cephalosporin derivatives, five aminoglycoside antibiotics, two lincomycins, two polymyxins, chloramphenicol and fucidin, appeared practically ineffective in vitro. Effectiveness of antimicrobials in vitro was considered on the basis of standard bioavailability of antimicrobial agents. No differences in antibiotic-susceptibility patterns of any practical significance were found, when strains isolated in Poland and Federal Republic of Germany were compared.

Anti-Bacterial Agents

Susceptibility of clinically important gram-negative bacilli to 15 antibiotics. Comparison of patterns in Poland and Federal Republic of Germany.

Three hundred and sixty strains of Gram-negative bacilli (Escherichia coli, Salmonella enteritidis, Enterobacter cloacae, Providencia, indole-positive and indole-negative Proteus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens), were isolated by random in Poland and Germany, and tested by agar dilution method for susceptibility to 15 antimicrobial agents, including six cephalosporin derivatives, colistin, gentamycin and tobramycin, three newer tetracyclines, ampicillin and carbenicillin, and a combination of trimethoprim and sulfamethoxazole. This investigation revealed existence of growing antibiotic-resistance of Gram-negative bacilli to all antimicrobial agents. A detailed analysis of this problem is described and a list of agents effective in vitro is presented. Some evidence has been found concerning possible existence of geographical differences in antibiotic-susceptibility patterns of strains of Gram-negative bacilli, isolated in Poland and Federal Republic of Germany.

Anti-Bacterial Agents