PubMed Health⌕ Search

Biomedical subjects

M Lyte

Publications and source records attributed to M Lyte.

43 records · Page 3Linked to original sources

Regulation of interleukin-1 production in murine macrophages and human monocytes by a normal physiological constituent.

The in vitro production of large quantities of interleukin-1 (IL-1) in mouse peritoneal exudate macrophages and human peripheral blood monocytes is possible through the use of the proteolytic enzyme pepsin and its zymogen pepsinogen. Equal amounts of IL-1 are generated by pepsin in the absence or presence of polymixin B. The addition of pepsin or pepsinogen had no effect on the proliferation of C3H/HeJ thymocytes to the plant mitogen phytohemagglutinin. Pepsin and pepsinogen are present in significant quantities in immune cells and the plasma. Although little is known concerning the physiological role of pepsin and pepsinogen outside of the gastrointestinal system, it may be proposed that the in vivo production of IL-1 may in part be regulated by the cellular and plasma concentrations of pepsin and pepsinogen.

Animals↗

Modulation of interleukin-1 production by macrophages following benzo(a)pyrene exposure.

The effects of benzo(a)pyrene (BaP), a highly prevalent environmental carcinogen, on the ability of peritoneal exudate macrophages to produce the secretory immunomodulatory molecule interleukin-1 (IL-1) in vitro was examined. A dose-dependent increase in lipopolysaccharide stimulated IL-1 production concomitant with decreased cell viabilities was noted in macrophages cultured in the presence of BaP. Antibody responses which are suppressed in BaP dosed mice can be reconstituted in vitro by the addition of exogenous interleukin-1. These results indicate that one of the cellular targets of BaP induced immunosuppression may be cells of the macrophage-monocyte lineage. Furthermore, BaP induced suppression of antibody responsiveness may be a result of alterations in production of IL-1.

Animals↗

Immunomodulation by polyaromatic hydrocarbons in mice and murine cells.

Several functionally defined in vitro antibody generating systems were used to assess the immunomodulating mechanisms of the benzopyrenes. When benzo(a)pyrene (BaP) or benzo(e)pyrene (BeP) was incorporated into a T-dependent antibody (TDAb)-producing spleen cell culture system, dose- and time-dependent inhibition of plaque-forming cell responses was observed. Addition of BaP at concentrations as low as 0.002 microgram/ml (7.93 nM) resulted in suppression of the TDAb plaque-forming cell response. BeP-induced suppression was seen at the 2-microgram level (7.93 microM). Time course evaluations demonstrated an early requirement for either chemical in culture in order to induce significant suppression. In vitro incorporation of BaP and BeP into polyclonal antibody-generating cultures also resulted in a dose-related inhibition. Inhibition of these antibody responses was also noted following in vivo exposure of mice to BaP or BeP. Fourteen-day exposure of mice to BaP (40 mg/kg) resulted in 98% suppression of the TDAb response. Polyclonal antibody responses were reduced 50 to 66% following 7 days of chemical exposure. BeP caused 51% suppression of the TDAb response following 14-day exposure of animals. These studies indicate that the suppressive effects of the benzopyrenes are multicellular in origin, occur apart from the carcinogenic effects of the chemicals, and cannot be attributed merely to cellular toxicity.

Animals↗

Differential immunotoxic effects of the environmental chemical benzo[a]pyrene in young and aged mice.

Young (3-6 months), middle-aged (16-18 months) and aged (23-26 months) mice were exposed in vitro and in vivo to the immunotoxic environmental chemical benzo[a]pyrene. The generation of antibody producing cells to the T-dependent antigens of sheep erythrocytes was observed to be suppressed in all age groups. Significantly, aged mice were shown to exhibit a greater percent suppression of antibody responses than young or middle-aged mice both in vitro and in vivo. The results presented provide the first evidence that the degree of immunological toxicity of environmental chemicals may be partially dependent upon the chronological and immunological age of the animal.

Age Factors↗

A special lipid mixture for membrane fluidization.

The potency for membrane fluidization of mixtures containing neutral lipids (NL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) from hen egg yolk was tested on human erythrocytes and lymphocytes. A specific mixture consisting of 70% NL, 20% PC and 10% PE was found to be a potent membrane fluidizer operating almost exclusively by extracting membrane cholesterol. Spectral results and electron micrographs indicate that aqueous dispersion of this mixture consists of chylomicron-like assemblies where the neutral lipids provide the hydrophobic core on the surface of which phospholipids are spread as a monolayer.

Drug Combinations↗

The effects of membrane modification and hyperthermia on the survival of P-388 and V-79 cells.

Cells with greater membrane microviscosities are reportedly less sensitive to being killed by mild hyperthermia. To further study this phenomenon, membrane microviscosity of ascites P-388 tumor cells was increased by adding cholesteryl hemisuccinate (CHS). Unexpectedly, when modified cells were heated for 60 min at 43 degrees C in vitro and analyzed in vivo in CDF1 mice they showed an increased thermal sensitivity. Similar increases in cell membrane microviscosity were obtained with V-79 cells. However, after heat treatment no differences in survival in vitro were noted between modified and unmodified cells. Treatment with CHS alone results in a substantial increase in P-388 cells, which take up trypan blue, but not in V-79 cells. When these 'dead' cells are accounted for, the difference in killing between control and CHS-modified P-388 cells is no longer seen. When considered in this light, both P-388 and V-79 cells are similar in their response to heat, which is not influenced by CHS per se.

Animals↗

Cholestryl-phosphoryl-choline in lipid bilayers.

Cholesteryl-phosphoryl-choline (CPC), a hybrid between cholesterol and lecithin, is incorporated into sonicated liposomes and erythrocyte membranes similarly to cholesterol. The effect of CPC on lipid microviscosity and degree of order is smaller, but not significantly than that of cholesterol. It is proposed that CPC may be employed as an efficient modulator of lipid dynamics.

Blood↗