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K L Erickson

Publications and source records attributed to K L Erickson.

At least 91 records · Page 5Linked to original sources
PubMed1988

Inability of murine peritoneal macrophages to convert linoleic acid into arachidonic acid. Evidence of chain elongation.

Various murine macrophage populations synthesize and secrete large amounts of arachidonic acid (20:4n-6) derived eicosanoids (cyclo-oxygenase and lipoxygenase products). These metabolites are known to possess a wide variety of functions with regard to the initiation and regulation of inflammation and tumorigenesis. Because the dietary intake of 20:4n-6 is usually low, tissues are largely dependent upon dietary linoleic acid (18:2n-6) as an initial unsaturated precursor for the biosynthesis of 20:4n-6. The purpose of these experiments was to determine whether resident or responsive murine macrophages possess desaturase and elongase activities capable of in vitro conversion of 18:2n-6 into 20:4n-6. Peritoneal exudate macrophages were purified by adherence and incubated in serum-free medium containing fatty acid-free BSA with [1-14C] 18:2n-6. Approximately 90 to 98% of the [14C]18:2n-6 at 4 and 16 h was recovered in phosphatidylcholine and phosphatidylethanolamine. The metabolism of [14C]18:2n-6 was determined after transesterification and separation of the 14C-fatty acid methyl esters by argentation TLC, reverse phase HPLC, and electron impact gas chromatography/mass spectrometry. Resident and responsive macrophages lacked the capacity to transform [14C]18:2n-6 into 20:4n-6. In addition, prelabeled macrophages incubated with soluble, calcium ionophore A23187 or phorbol myristate, or particulate, zymosan, membrane perturbing agents also lacked delta 6 desaturase activity. All macrophages tested were capable of elongating [14C]18:2n-6 into [14C]20:2n-6. These observations suggest that 20:4n-6, present in macrophage phospholipids, is biosynthesized elsewhere and transported to the macrophage for esterification into the phospholipids. In addition, these findings demonstrate that elongase activity is present in both the resident and responsive peritoneal macrophage.

Acetyltransferases↗
PubMed1988

Dietary manipulation of macrophage phospholipid classes: selective increase of dihomogammalinolenic acid.

Because alterations in the dietary content of fatty acids are an important method for modulating macrophage eicosanoid production, we have quantitated the levels of n-6 and n-3 polyunsaturated fatty acids in peritoneal macrophage individual phospholipids from mice fed diets (3 wk) with either safflower oil (SAF), predominantly containing 18:2n-6, borage (BOR) containing 18:2n-6 and 18:3n-6, fish (MFO) containing 20:5n-3 and 22:6n-3, and borage/fish mixture (MIX) containing 18:2n-6, 18:3n-6, 20:5n-3 and 22:6n-3. Dietary n-3 fatty acids were readily incorporated into macrophage phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI). The increase in n-3 fatty acid levels was accompanied by a decrease in the absolute levels of 18:2n-6, 20:4n-6 and 22:4n-6 in PC, PE and PS. Interestingly, PI 20:4n-6 levels were not significantly lowered (P greater than 0.05) in MIX and MFO macrophages relative to SAF and BOR. These data demonstrate the unique ability of this phospholipid to selectively maintain its 20:4n-6 levels. In BOR and MIX animals, 20:3n-6 levels were significantly increased (P less than 0.05) in all phospholipids relative to SAF and MFO. The combination of borage and fish oils (MIX diet) produced the highest 20:3n-6/20:4n-6 ratio in all phospholipids. These data show that the macrophage eicosanoid precursor levels of 20:3n-6, 20:4n-6 and n-3 acids can be selectively manipulated through the use of specific dietary regimens. This is noteworthy because an increase in phospholipid levels of 20:3n-6 and 20:5n-3, while concomitantly reducing 20:4n-6, may have therapeutic potential in treating inflammatory disorders.

8,11,14-Eicosatrienoic Acid↗
PubMed1988

Fatty acid composition of macrophage phospholipids in mice fed fish or borage oil.

The polyunsaturated fatty acid (PUFA) composition of murine peritoneal macrophage phospholipids was dramatically altered in vivo following the four-wk feeding of specific dietary oils. Fish oil (containing 20:5n-3 and 22:6n-3) feeding significantly increased macrophage 20:5n-3, 22:5n-3, and 22:6n-3 (P less than 0.05), while borage oil (containing 18:2n-6 and 18:3n-6) increased (P less than 0.05) the macrophage 20:3n-6/20:4n-6 ratio, relative to safflower oil (containing 18:2n-6) and hydrogenated coconut oil (containing 12:0)-fed animals. The macrophage phospholipid PUFA profiles were compared with those of the liver, lung and spleen. The significance of the PUFA alterations is discussed.

Animals↗
PubMed1987

Enhancement of metastasis from a transplantable mouse mammary tumor by dietary linoleic acid.

The influence of quantitative differences in dietary linoleic acid (18:2) on the metastasis as well as the development of line 4526 mouse mammary tumors was investigated. High fat diets (20%, w/w) that contained either 1, 2, 4, 8, or 12% 18:2 by weight, were prepared by using mixtures of coconut and safflower oil and fed to female BALB/c mice that were subsequently inoculated with 10(4) 4526 tumor cells s.c., either at the lateral abdominal wall (LAW) or in the mammary fat pad (MFP). Latency of LAW tumors was influenced by the level of dietary 18:2, whereas the latency of MFP tumors was not. When metastasis was assessed, mice with MFP tumors fed 1, 2, 4, or 8% 18:2 diets had 62-73% fewer lung surface tumor nodules than similar mice fed 12% 18:2. Mice in all dietary groups with LAW tumors had fewer metastatic lung nodules than mice with MFP tumors; mice with LAW tumors fed diets containing 1, 2, or 4% 18:2 had 52-69% fewer nodules than similar mice fed diets containing 8 or 12% 18:2. There were no significant differences in the rate of increase of body weight or the daily mean tumor volumes when compared with dietary 18:2 level. Fatty acid composition of the tumor, particularly the level of 18:2, was significantly altered by diet. This study demonstrates that while the level of dietary 18:2 does not enhance the growth rate of primary 4526 tumors and does or does not affect the latency depending on the primary site, it does significantly alter the metastasis. These results stress the importance of metastasis assessment in future studies involving dietary fat effects on tumorigenesis.

Animals↗
PubMed1987

Dietary fat modulation of murine mammary tumor metabolism studied by in vivo 31P-nuclear magnetic resonance spectroscopy.

The effect of dietary fat concentration and saturation on high energy phosphate metabolites and phospholipid turnover in transplanted line 168 murine mammary tumors was studied using surface coil 31P-nuclear magnetic resonance spectroscopy. Female BALB/c mice were fed one of five diets each containing at least the minimum of essential fatty acids (EFA). Four diets contained additional safflower or palm oil for a total fat concentration of 5 or 20% by weight. The growth rate of tumors from mice fed the high safflower oil diet was significantly greater than the growth rate of tumors for mice fed all other diets including the one which contained the minimal EFA. 31P-nuclear magnetic resonance-observable phosphate metabolite ratios. ATP/Pi, ATP/phosphomonoester (ATP/PME), and PME/Pi, and tumor pH of line 168 tumors decreased with increasing tumor volume, indicating a shift from active to inactive tumor metabolism. The rates of those decreases with progressive tumor growth differed significantly among tumors of mice fed the different diets. Decreases in ATP/Pi, ATP/PME, and pH were the most rapid in the tumors of mice fed the high safflower oil diet and significantly faster than tumors of mice fed the diet containing minimum EFA. In addition, the decrease in the PME/Pi ratio of tumors was significantly greater in mice fed the high fat (high palm oil and high safflower oil) diets than mice fed the diet containing the minimum of EFA. The rate of decline of ATP/Pi and ATP/PME with progressive tumor growth was directly correlated with levels of linoleic acid as well as total unsaturated fat. High levels of a polyunsaturated fat had a significant effect on mammary tumor metabolism particularly during early stages of tumor growth. Differences in high energy phosphate metabolite dynamics relative to dietary fat were present in tumors of equal volume. Thus, dietary fat influences on mammary tumorigenesis may be related to high energy phosphate metabolites.

Adenosine Triphosphate↗
PubMed1987

Influence of dietary fats on cell populations of line 168 mouse mammary tumors: a morphometric and ultrastructural study.

The effect of dietary fat concentration and saturation on cell composition and structure of line 168 mouse mammary tumors in vivo was studied using morphometry and electron microscopy. Both the concentration and saturation of fat fed to mice had a significant influence on the volume ratio of mast cells infiltrating line 168 tumors. Tumors of mice fed diets containing a high concentration (20%) of either safflower oil (SO) or palm oil (PO) had 2-3 times the volume ratio of mast cells than mice fed diets containing a low concentration (5%) of either fat. There were no significant differences among diets with respect to other inflammatory cell populations. Mice fed either one of the high fat diets had tumor cells with inclusions that ultrastructurally, appeared to consist of lipid. Dietary fat, however, had no observable affect on cell junctions or other morphological characteristics. Greater infiltration of mast cells in tumors of mice fed high fat diets and the eventual formation of new blood capillaries may explain the decreased latency of tumor onset and enhanced growth of tumors in mice fed diets with high concentrations of fat.

Animals↗
PubMed1986

Kappa opioid receptor-mediated analgesia in the developing rat.

The prototypic kappa opiate ketocyclazocine produced robust analgesia in 10-day-old rats in the tail-flick nociceptive test. The kappa-opiate behavioral response coincided with the onset of a rapid rise to adult levels in brain kappa receptor site density. In contrast, morphine (prototypic mu opiate) was without marked effect until 14 days of age. The period of rapid mu receptor increase did not take place until days 14-16, which was after kappa receptor levels had already plateaued. Further, there was no or incomplete cross-tolerance between ketocyclazocine and morphine at 14 days of age. The present study, therefore, establishes a role for the kappa binding site in thermal analgesia in the tail flick test and differentiates its ontogenetic pattern from that of the mu receptor.

Age Factors↗
PubMed1986

Dietary fatty acid modulation of murine B-cell responsiveness.

These studies were designed to determine how dietary fat concentration and degree of saturation influence antibody response to a T-dependent antigen. In vivo fatty acid manipulation did not affect the total number of nucleated spleen cells or IgM or IgG-bearing cells. After primary immunization with sheep red blood cells (SRBC), the number of splenic IgM and IgG antigen specific plaque-forming cells (PFC) was lower in mice fed a diet containing a high level of polyunsaturated fat (PUF, safflower oil) than in mice fed a diet containing minimal essential fatty acids (EFA, 0.5% corn oil). Mice fed a high level of saturated fat (SF, coconut oil) exhibited greater IgM PFC responses than the control. After secondary immunization, the number of IgG-producing cells followed a similar response pattern. These differences were also reflected in the serum anti-SRBC IgM and IgG levels as determined by solid-phase radioimmunoassay. Although the level of linoleic acid in whole lymphocytes has been previously reported to change in direct relation to the serum fatty acid level, no differences in the fatty acid composition of isolated lymphocyte plasmalemma were observed. Thus, changes in the number of antibody-forming cells appear to be inversely related to the levels of linoleic acid in other cell compartments. Fluorescence polarization measurements of the lipopholic probe, 1, 6-diphenyl-1,3,5-hexatriene (DPH), in the purified lymphocyte plasmalemma from mice fed a diet high in PUF indicated an increase in mobility. Polarization values for lymphocyte plasmalemmas from mice receiving diets high in SF were not significantly different from the controls. We conclude that dietary fat modulation of splenic B-cell responses was manifested through changes in the number of cells producing antibody and level of antibody produced, not through total splenic B-cell numbers. This B-cell response can be modified, depending upon the fatty acids available to the cell, and may be related to differential effects upon plasma membrane structure.

Animals↗
PubMed1986

Gestational immunosuppression is mediated by specific Lyt 2+ T cells.

Female BALB/c mice were tested during the first week of pregnancy for their lymphocyte-mediated cytotoxic response to paternal alloantigens. Spleen or uterine regional lymph node cells were not spontaneously cytotoxic against concanavalin A-activated paternal target lymphocytes. Female mice immunized i.p. with paternal H-2-matched or third-party allogeneic cells on the fifth day and tested on the 12th day of pregnancy demonstrated total suppression of cell-mediated cytotoxicity to paternal alloantigens and partial suppression to third-party alloantigens. A generalized non-specific immunosuppression to alloantigens seems to be associated with pregnancy, which may indicate that soluble factors were involved in mediating the suppressive effect. Cocultures of spleen cells from virgin mice and the whole population of spleen or regional lymph node cells from allogeneic pregnant female mice demonstrated specifically suppressed responses to alloantigens. Similar cocultures with Thy 1.2- and Lyt 2.2-depleted populations restored the cytotoxicity levels of activated spleen cells. We conclude that antigen-specific Lyt 2+ T cells were activated during pregnancy to regulate the female T-cell response to paternal alloantigens.

Animals↗
PubMed1985

Plasma membrane isolation and fatty acid analysis of membrane lipids from murine lymphocytes.

Plasma membranes have been isolated in high yield by a novel method from splenic lymphocytes of BALB/c mice. These membranes were purified in predominantly envelope form, essentially right-side out, by zinc stabilization and sucrose density gradient centrifugation. A simple, rapid method was used for derivatization and analysis of fatty acids in plasma membrane lipids.

Animals↗
PubMed1985

Dietary fatty acid modulation of murine T-cell responses in vivo.

The effect of dietary fat concentration and saturation on T-cell functions in vivo were investigated by using delayed-type hypersensitivity (DTH) and graft-versus-host (GVH) reactions. These were selected because they circumvent the problem of fatty acid flux from the lymphocyte during in vitro assays. The DTH reaction to allogeneic line B16-BL6 melanoma cells was suppressed in BALB/c mice fed a diet containing 20% saturated fat (coconut oil) or polyunsaturated fat (safflower oil) compared to control mice fed a diet with the minimum of essential fatty acids (EFA). Likewise, DTH responsiveness of mice fed an EFA-deficient diet was less than that of mice fed the EFA control diet. The GVH reaction of C57BL/6 spleen cells injected into irradiated BALB/c mice was suppressed in those fed 20% polyunsaturated fat. Serum levels of linoleic acid increased commensurate with the levels of polyunsaturated fat in the diet. Likewise, previous work has demonstrated that levels of linoleic acid in whole lymphocytes changed in direct relation to the levels of fatty acids in serum and the diet. Thus, T-cell functions in vivo may be differentially affected by the degree of saturation or the concentration of dietary fat. Moreover, linoleic acid appears to play a pivotal role in modulating cellular immune responses.

Animals↗
PubMed1985

Susceptibility of mammary tumor cells to complement-mediated cytolysis after in vitro or in vivo fatty acid manipulation.

The susceptibility of line 168 murine mammary tumor cells to complement (C)-mediated lysis was tested after in vitro treatment with several saturated or unsaturated fatty acids dissolved in different solvents or presented in the form of micelles to the cells. The lytic susceptibility of these cultured cells was compared with similar tumor cells obtained either from mice maintained on diets containing different concentrations and saturations of fatty acids or from cultures supplemented with serum from tumor-free control mice fed pair-matched diets. Although changes in dietary fat concentration and saturation resulted in alterations of the tumor cell fatty acid composition, those alterations did not influence the susceptibility of tumor cells to C-mediated lysis. However, single, or combinations of, unsaturated fatty acids dissolved in ethanol, unlike saturated fatty acids, reduced the lytic susceptibility of tumor cells in vitro. Hexane added to culture medium significantly suppressed the lytic susceptibility; however, when used as a carrier no significant differences were observed among treatments with the individual fatty acids at several concentrations. This result may be due to the effect of hexane on the cell membrane because this treatment also affected the osmotic fragility of the cells. Fatty acids as micelles did not influence the susceptibility of tumor cells to lysis. We concluded that only in vitro manipulation of fatty acids in some vehicles influenced the susceptibility of target tumor cells to C-mediated lysis; this finding did not parallel the situation that occurred in vivo. Moreover, the use of different vehicles to present fatty acids to tumor cells may further alter the susceptibility to C-mediated lysis.

Animals↗
PubMed1985

Lipid modulation of mammary tumor cell cytolysis: direct influence of dietary fats on the effector component of cell-mediated cytotoxicity.

For understanding the mechanism by which fatty acids promote mammary tumor growth, experiments were designed to determine the influence of dietary fat concentration and saturation on both effector (Ef) and target (Ta) cells in an allogeneic antitumor cell-mediated immune response. Exposure of cytotoxic T-lymphocytes (CTL) to different fatty acids led to significant changes in the subsequent cytolytic capacity of these cells after both primary and secondary immunization. An increase in both saturated (SF) and polyunsaturated (PUF) fats led to decreased cytotoxic function after primary immunization. After a secondary challenge, the suppressive influence of SF was significantly greater than that of PUF, compared to that of the control diet containing essential fatty acids as the only fat source. This response was mediated by a direct effect on the CTL and not through an increase in suppressor or a decrease in Ef or helper cell frequency. In contrast, manipulation of the fatty acid environment of the Ta mammary tumor cells in vivo or in vitro had no significant effect on their susceptibility to lymphocyte-mediated cytotoxicity. Therefore, dietary fats may mediate their effect by a direct influence on the immunocompetent lymphocyte and not on the Ta mammary tumor cell.

Animals↗
PubMed1984

Influence of dietary fatty acid concentration and geometric configuration on murine mammary tumorigenesis and experimental metastasis.

To investigate the influence of fatty acid geometric isomers on the growth and experimental metastasis of mammary tumors, mice were fed diets containing fat high in either cis or trans fatty acids. The cis fat was prepared to have a fatty acid composition similar to that of the trans fat; both were provided at 5 or 20% (by weight) of the diet. Line 168 mammary tumor cells were transplanted: 1) subcutaneously into female BALB/c mice to observe the effects of dietary fat on latency and local tumor growth, and 2) intravenously to observe influences on experimental metastasis. No differences in the latency or rate of primary tumor growth were observed among the groups fed the diets containing cis or trans fatty acids. In addition, there were no differences in fatty acid composition except the levels of trans-C18:1 in the primary tumor cells among the groups fed the experimental diets. Livers and spleens from animals fed both the 5 and 20% cis diet contained significantly more viable radiolabeled tumor cells than those fed the trans diets. Although body weight and composition were not significantly different among the groups, livers from animals fed the diets containing trans fatty acids were significantly heavier than those fed diets containing only cis fatty acids. Thus, trans fatty acids behaved similarly to cis fatty acids with respect to promotion of transplantable mammary tumor growth but trans fatty acids were less effective than cis fatty acids in promoting the blood-borne implantation and distant survival of the tumor cells.

Animals↗
PubMed1984

Dietary fat influences on murine melanoma growth and lymphocyte-mediated cytotoxicity.

The effects of fat concentration and saturation on the growth of a B16 melanoma and lymphocyte-mediated cytotoxicity against the cells were studied with the use of inbred C57BL/6J and C3H/HeJ mice subjected to dietary manipulation before and after tumor transplantation. The tumor latency for mice initially given injections of 5 X 10(6) syngeneic B16 melanoma cells was significantly less for those mice fed at 20% fat concentration than those fed only the essential fatty acid (EFA) diet. When mice were given injections of 10(6) melanoma cells, the initiation time required for visible tumor growth in mice receiving the polyunsaturated fat (PUF) diet was significantly less than that in mice receiving the saturated fat (SF) diet. Cytolysis mediated by lymphocytes from diet-manipulated mice toward allogeneic B16 melanoma cells was greater for those mice receiving the EFA diet only and 8% SF diets than for those mice fed a diet without fat. The cytolytic response decreased immediately with the additional PUF in the diet, whereas additional SF decreased cytolytic responses only when dietary SF concentration was greater than 8%. Thus dietary fat, particularly PUF, has a significant influence on the growth and lymphocyte-mediated cytotoxicity of a murine melanoma. This effect cannot be attributed to differences in the energy content between high-fat and low-fat diets.

Animals↗
PubMed1984

Seminal plasma inhibits lymphocyte response to T-dependent and -independent antigens in vitro.

The effect of seminal plasma, epididymal spermatozoa, or whole semen on antibody producing cells was examined in vitro after (i) direct culture with spleen or B cells, and (ii) cocultivation of B cells with T cells previously incubated with seminal plasma. Seminal plasma, and not epididymal spermatozoa, have an inhibitory effect on the direct hemolytic plague forming cell response. This was mediated by a direct inhibitory effect on the B cell and not through the generation of suppressor T cells as demonstrated by responses to T-independent and -dependent antigens. Thus, the mode of suppressive action of seminal plasma in vitro is probably different from that previously reported in vivo.

Animals↗