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K Krzystyniak

Publications and source records attributed to K Krzystyniak.

59 records · Page 4Linked to original sources

Suppression of avidin processing and presentation by mouse macrophages after sublethal exposure to dieldrin.

The molecular events in macrophage antigen processing and presentation were examined to determine the possible site(s) of cell-xenobiotic interaction. Antigenic processing by mouse peritoneal macrophages of a single protein antigen, avidin, was significantly suppressed following sublethal exposure of animals to an organochlorine pesticide, dieldrin. Exposure of C57B1/6 female mice to dieldrin affected the in vitro uptake of [methyl-14C]avidin by peritoneal macrophages and markedly decreased phagocytosis of fluorescein-labelled microspheres and Salmonella typhimurium. Release of the processed avidin, determined by immunochemical quantification of immunogenic avidin and by bioassay of immunogenicity of the released antigen, was also markedly affected. Dieldrin markedly affected presentation of avidin on the macrophage surface, observed by cytoimmunochemical staining of the antigen with fluorescent antibody and flow cytometry. Inhibition of the release of processed avidin was dieldrin dose- and time-dependent, following single sublethal intraperitoneal (ip) exposure to the pesticide. The antigenic properties of processed avidin, determined by biological assay using lymphocyte cultures of normal C57B1/6 mice primed with avidin, were proportional to the antigen concentration in supernatants of macrophage cultures, for both vehicle controls and dieldrin-exposed animals. This observation and analysis of the kinetics of release of processed avidin by macrophages from control and dieldrin-exposed animals suggested that the release of processed avidin, but not the immunogenicity of the antigen itself, was affected by the pesticide exposure. Generally, impairment of avidin processing and presentation appeared to be more dramatic than other pesticide-related injuries to macrophages, such as the uptake of the antigen. In conclusion, antigen processing could be a sensitive target for dieldrin-related injury of macrophage functional activities, which, in consequence, could produce suppression of the humoral immune response.

Animals↗

In vitro lymphotoxicity and selective T cell immunotoxicity of high doses of acyclovir and its derivatives in mice.

The antiviral drug acyclovir [9-(2-hydroxyethoxymethyl)guanine (ACV)], its 7-isomer (7-ACV) and its two derivatives: N2-acetyl ACV (ac-ACV) and N2,O-diacetyl ACV (diac-ACV) were examined for their potential in vitro lymphotoxicity and in vivo immunotoxicity in mice. In vitro lymphotoxicity of ACV and its acetylated derivatives was low, whereas the 7-ACV isomer enhanced the in vitro cell proliferation in PHA-stimulated cultures. Addition of 2'-deoxyguanosine (dGuo) did not exhibit any inhibitory potential of ACV. However, reduction in the absolute number of CD3+, CD8+, and CD25+ cells, but not Ig+ cells, was noted at high concentrations of ACV and its derivatives, suggesting a selective T cell cytotoxicity. Similarly, the in vivo exposure revealed selective T cell immunotoxicity of ACV and its derivatives since the reduced number of Thy 1.2+ and CD8+ cells was not accompanied with any marked changes in the Ig+ population. The CD4+/CD8+ ratio was affected both in vitro and in vivo by high concentrations of ACV.

Acyclovir↗

In vivo indomethacin reverse exercise-induced immunosuppression in rats.

The effect of oral indomethacin on the immunosuppressive effect of exercise was examined in exercised untrained female Wistar rats immunized with sheep red blood cell (SRBC) antigens. Intensity of the 1 h exercise was controlled by 0-50 kPa air pressure, generated by a compressor located at the bottom of a water tank, during continuous swimming of the rats, previously immunized with SRBC. After 48-72 h, depending on the ip (intraperitoneal) or iv (intravenous) route of SRBC immunization, the exercise suppressed humoral PFC response and augmented phagocytosis of peritoneum macrophages. These effects occurred only when exercise was performed at 48 h after antigen injection. Animals receiving indomethacin, however, did not show any exercise-related suppression of the PFC response. The data suggest a relationship between exercise-induced immunosuppression and possible increased in vivo prostaglandin synthesis during the intense exercise. Overall, exercise-related suppression of humoral PFC response was dependent on the intensity of the exercise, was time specific, and was reversible by pharmacological blockade of the cyclooxygenase pathway of prostaglandin synthesis.

Administration, Oral↗

Macrophage functional activities versus cellular parameters upon sublethal pesticide exposure in mice.

The toxicity of selected organochlorine, organophosphate, and carbamate pesticides on the functions and cellular parameters of peritoneal macrophages was examined in inbred C57Bl/6 mice. Effects of single, sublethal pesticide exposure on macrophages were determined by analysis of the cell viability, cell adherence capacity, generation of superoxide anion (O2-), antigen processing, phagocytosis of Salmonella typhimurium, and resistance to in vitro virus-induced cytopathic effects (cpe) after infection with mouse hepatitis virus 3 (MHV3). Most of the studies were done for the organochlorine pesticide dieldrin, which inhibited several macrophage functions, such as phagocytosis of S. typhimurium, release of the single processed protein antigen avidin, and resistance to MHV3 virus-induced cpe. The virus-induced cytolysis in macrophage cultures was significantly increased after in vivo exposure to single sublethal doses of other selected pesticides, such as guthion, carbofuran, sevin, and matacil. However, none of the selected pesticides, used in sublethal (0.4 less than or equal to LD50 less than or equal to 0.6) doses appeared to be a factor impairing the O2- -generating system in chemically elicited or immunologically activated peritoneal macrophages. In conclusion, sublethal pesticide exposure can induce a significant impairement of several macrophage functions, such as phagocytosis, antigen processing, and resistance to virus-induced cytolysis. Inhibition of the O2- -generating system by sublethal pesticide exposure, however, can be excluded as a mechanism of potential suppressory action of these pesticides on antiviral and antibacterial host defence systems in which macrophages play a primary role.

Animals↗