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Biomedical subjects

D C Morrison

Publications and source records attributed to D C Morrison.

At least 127 records · Page 7Linked to original sources
PubMed1985

The effect of bacterial lipopolysaccharide (LPS) on histamine release from human basophils. I. Enhancement of immunologic release by LPS.

Preincubation of human basophils with bacterial lipopolysaccharide (LPS) purified from the heptose-deficient mutant Salmonella minnesota R595 enhanced by an average of sixfold the response of peripheral blood basophils obtained from allergic donors to several allergens in vitro as judged by release of histamine. Enhancement occurred at suboptimal, optimal, and supraoptimal concentrations of antigen. No effect was seen if basophils were from a nonallergic donor, and LPS by itself rarely caused histamine release from any preparation of basophils. However, histamine release in basophils from nonallergic donors induced by antibody directed against IgE (anti-IgE) also was enhanced by LPS. Potentiation of histamine release occurred if basophils were pretreated with LPS before addition of anti-IgE for as little as 5 min; there was no increase in release if anti-IgE and LPS were added simultaneously to cells. LPS enhanced the rate of release without altering duration of the release response. LPS potentiation of release of histamine by F(ab')2 fragments of anti-IgE was equivalent to its effect on release triggered by the intact antibody molecule, confirming that the effect of LPS is not due solely to its interaction with the Fc component of the anti-IgE. These data thus provide evidence for modulation of basophil response to IgE-mediated stimuli by LPS, resulting in a significant enhancement of response. Enhancement by LPS appears to be independent of the stimulus which triggers the IgE receptor. The contribution of this mechanism to allergic disease or asthma remains to be determined.

Adjuvants, Immunologic↗
PubMed1985

Ganglioside modulation of lipopolysaccharide-initiated complement activation.

Highly purified preparations of mouse gangliosides have been demonstrated to bind to purified preparations of lipopolysaccharide (LPS). In some instances, the binding has been demonstrated to be dependent upon the presence of sialic acid in the ganglioside preparation. The binding of gangliosides to LPS from the deep rough Salmonella minnesota Re mutant has suggested that the interaction involves the lipid A-2-keto-3-deoxyoctulosanate region of the LPS macromolecule. The interaction between gangliosides and LPS has been demonstrated to result in an abrogation of lipid A dependent activation of the classical pathway of serum complement by Re LPS. Surprisingly, however, the presence of sialic acid containing glycolipids has been shown to enhance significantly the capacity of LPS to initiate activation of the alternative pathway of complement. These data suggest that sialic acid can enhance as well as inhibit the formation of a stable alternative-pathway C3 convertase.

Animals↗
PubMed1985

Mechanism of polymyxin B-mediated lysis of lipopolysaccharide-treated erythrocytes.

A novel system was used previously to characterize the dynamic interaction of a polysaccharide-deficient, lipid-rich lipopolysaccharide (LPS) with rabbit erythrocytes (RaRBC). Exposure of the RaRBC to the LPS rendered them sensitive to induction of hemolysis by the cationic antibiotic polymyxin B (PB) in a time- and temperature-independent manner. Subsequent decay in the response of LPS-sensitized cells to PB was shown to be critically dependent on both the time and temperature of incubation of RaRBC with LPS and to be independent of a change in LPS binding (Carr and Morrison, Infect. Immun. 43:600-606, 1984). In the present study, we performed experiments designed to define the mechanism by which PB mediates hemolysis of LPS-sensitized RaRBC. Experiments were performed to examine the molecular requirements of the LPS and the PB that were essential for hemolytic activity. The capacity of various cations to mediate hemolysis of LPS-sensitized RaRBC or to block PB-mediated hemolysis and the temperature dependence of the PB lytic reaction were investigated. The results of these experiments suggest that PB-mediated hemolysis of LPS-treated erythrocytes is dependent upon an initial ionic association of PB with erythrocyte membrane-bound LPS, followed by hydrophobic insertion of the PB fatty acid into the erythrocyte membrane lipid bilayer.

Animals↗
PubMed1985

Signs of neurobehavioral dysfunction in a sample of learning disabled children: stability and concurrent validity.

Of 270 learning disabled children with average intelligence and significant delays in reading comprehension a sample of 37 were evaluated for signs of neurobehavioral dysfunction. All such signs--primitive reflexes, equilibrium reactions, and postrotary nystagmus--were reliably assessed. A subsample of 19 children was compared with developmentally normal and mentally retarded samples for the occurrence of tonic neck reflexes and equilibrium reactions. The learning disabled children consistently showed deviancies like those of the retarded children; both of these groups differed from the normal children on most measures. These deviant responses persisted over a 9-mo. period for the learning disabled group. Compared with norms, the total learning disabled sample displayed hyponystagmus, and this depressed nystagmus persisted for 11 mo. Results are discussed in relation to the lack of correlation among the various signs of neurobehavioral dysfunction in the learning disabled children.

Achievement↗
PubMed1985

Lipopolysaccharide receptors on lymphocytes. I. Lack of immunologic recognition of a putative LPS receptor on LPS-responder lymphocytes by LPS-nonresponder mice.

We have examined the potential immunogenicity of viable lymphocytes from C3HeB/FeJ responder mice adoptively transferred into congenic nonirradiated C3H/HeJ nonresponder mice. Immunologic rejection or acceptance of donor cells was employed as indirect evidence for the presence or absence of an antigenically distinct "LPS receptor" present on donor lymphocytes. Immunogenicity was evaluated by in vitro assessment of the subsequent proliferative response of recipient splenocytes to protein-free LPS after multiple i.p. injections of responder lymphocytes. Control experiments have made use of syngeneic donor lymphocytes differing immunologically by the presence of the H-Y minor histocompatibility antigen. The results of these experiments provide evidence for the concept that if the phenotypic difference between LPS responder and nonresponder mice is also expressed antigenically in the form of an LPS receptor, that antigenic difference is significantly less immunogenic than a minor histocompatibility antigen.

Animals↗
PubMed1985

Activation of murine spleen cells by lipid A: negative modulation of lipid A mitogenic activity by O-antigen polysaccharide.

We have investigated the regulatory effects of polysaccharide-rich subunits upon lipid A activity with the use of hybrid LPS macromolecules of defined subunit composition. Hybrid LPS were constructed with polysaccharide-rich LPS from Escherichia coli O55:B5 and lipid A-rich LPS from Salmonella minnesota R595 by dissociation of the two parental LPS species to monomeric solutions with deoxycholate, admixing these LPS in various proportions and reassociation into high m.w. LPS hybrid aggregates by removal of the deoxycholate. Isopycnic densities of LPS hybrids were intermediate to those of the two parental LPS species, confirming the formation of true hybrids. Murine spleen cell proliferative responses induced by hybrid LPS macromolecules were also intermediate to those obtained with parental LPS but significantly less than would be anticipated on the basis of total lipid A content. These results demonstrate that the polysaccharide portion of LPS can negatively regulate the expression of lipid A in LPS micellar aggregates.

Animals↗
PubMed1985

In vivo biological activities of endotoxin.

The basic mechanisms by which bacterial lipopolysaccharides (LPS) interact with cells and tissues of the endotoxin sensitive host have been examined within the context of defining critical targets for the manifestation of the multiple pathophysiologic effects of this potent bacterial toxin. Evidence has been presented to suggest that metabolic processing of bacteria by phagocytic cells can result in the release of biologically active endotoxin. The available experimental data would indicate that, in the mouse, a bone marrow derived radiosensitive cell is responsible for the toxic effects of endotoxin. The precise mechanism by which lipopolysaccharides interact with these cells remains to be elucidated. Although interaction with critical targets on the membrane of LPS responsive cells is established, the evidence for specific endotoxin receptor molecules is weak and still controversial. Recent data suggest that, if such endotoxin receptors do, in fact exist, they are at best only weakly immunogenic. The use of the C3H/HeJ "endotoxin unresponsive" mouse strain, however, remains as an extremely useful experimental model to define the mode of action of endotoxin at the molecular level.

Animals↗
PubMed1984

Ocular localization of circulating bacterial lipopolysaccharide.

A bacterial lipopolysaccharide (LPS) extracted from a rough strain of Salmonella minnesota ( Re595 ) containing primarily lipid A was used to study tissue distribution following its intravenous injection in rabbits. For this purpose, the Re595 was either labelled with 125iodine (125I) and localization quantitated by gamma radiation spectrometry and radioautography of different tissues or a fluorescein labelled antibody to Re595 was employed. Localization of [125I]- Re595 or LPS was looked for at 30 min and 2 hr after intravenous injection. [131I]-albumin was employed either to measure intravascular protein or total tissue protein and, in some studies, [131I]-albumin and [125I]-fibrinogen were used to measure protein after unlabelled Re595 . Both fractions of isotopes injected and estimates of tissue-bound Re595 were made in the whole eye, liver, spleen, kidney and lung and in isolated iris-ciliary processes, aqueous, lens, vitreous, and posterior segment (retina, choroid, and sclera). Aqueous and iris-ciliary processes, but no other tissues, showed a marked extravazation of [131I]-albumin and [125I]-fibrinogen. [125I]- Re595 was found to localize primarily in liver and spleen. At 30 min, [125I]- Re595 was found in nanogram quantities within the eye and at 2 h greater amounts of LPS were found in iris-ciliary processes and aqueous than in the posterior segment. Neither radioautography nor fluorescein-labelled antibody to Re595 showed evidence of histologic localization of LPS in the iris-ciliary processes. These results indicate that although LPS does not localize preferentially in the eye, it does accumulate in quantities sufficient to have an effect locally.

Animals↗
PubMed1984

Selective association of lipid-rich R-like lipopolysaccharide subunits with murine spleen cells.

SDS-PAGE was used to analyze the subunit composition of 125I-lipopolysaccharide (LPS) in the cell-associated and supernatant fractions of murine spleen cells after culture with radiolabeled LPS from the smooth strain of E. coli O55:B5. Quantitative estimates from densitometric scans of autoradiographs indicated that certain R-like subunits were selectively enriched in cell-associated fractions by a factor of 2.8 as compared to native O55 LPS. Coincident with this selective enrichment was a 57% decrease in these subunits in supernatant fractions. In contrast, the level of polysaccharide-containing subunits in cell-associated fractions was equivalent to or less than the corresponding subunit in native LPS. LPS bound at 37 degrees C was capable of eliciting a significant B-lymphocyte proliferative response in responder spleen cells. However, this selective binding of lipid-rich R-like subunits to splenocytes is insufficient, by itself, to initiate a triggering event since it is both quantitatively and qualititatively indistinguishable in lymphoid cells from the LPS responder (C3HeB/FeJ) mouse and the LPS non-responder (C3H/HeJ) mouse.

Animals↗
PubMed1984

Lipopolysaccharide interaction with rabbit erythrocyte membranes.

In this study we have characterized the association of a polysaccharide-deficient, lipid-rich lipopolysaccharide (LPS) with rabbit erythrocytes (RaRBC). With polymyxin B sulfate-mediated hemolysis as a probe, we have shown that Salmonella minnesota R595 LPS interacts with RaRBC in two distinguishable steps. The first step whereby RaRBC exposed to LPS are rendered sensitive to polymyxin B-initiated lysis probably represents absorption of LPS to the RaRBC membrane. We investigated two possible mechanisms for the subsequent time-dependent decrease in response of LPS-treated RaRBC to polymyxin B. We found that the decay in polymyxin B susceptibility of LPS-treated RaRBC cannot be attributed to a decrease in binding of LPS to the RaRBC. On the other hand, our results are consistent with a time-dependent rearrangement of the amphipathic LPS within the lipid bilayer of the RaRBC membrane. In particular, at lower incubation temperatures of RaRBC and LPS, the decay in polymyxin B-induced hemolysis is slower, presumably, because the increased membrane viscosity allows less rapid rearrangement of LPS within the lipid bilayer. A putative hydrophobic intercalation of LPS into a mammalian cell membrane may be of importance in LPS stimulation of responsive cells.

Absorption↗
PubMed1984

The fate of E. coli lipopolysaccharide after the uptake of E. coli by murine macrophages in vitro.

The fate of bacterial lipopolysaccharide (LPS) after the uptake of Escherichia coli by macrophages in vitro was studied. The LPS of the galactose epimerase-deficient E. coli J5 mutant was specifically radiolabeled with [3H]galactose by growing the organism in a basic salts medium containing galactose. Control bacteria were uniformly radiolabeled by growth in [14C]glucose and unlabeled galactose-containing medium. Surface constituents of E. coli were also labeled with 125I. After in vitro phagocytosis of labeled E. coli by murine peritoneal exudate macrophages, the rate of exocytosis of LPS, as assessed by release of 3H over a 72-hr period, was considerably reduced in comparison with other bacterial constituents (14C and 125I release). The [3H]galactose-labeled material exocytosed from macrophages and that remaining intracellularly (obtained from macrophage lysates) were isolated by cesium chloride (CsCl) density gradients and were shown to have altered density profiles as compared with purified E. coli LPS. The macrophage-"processed" [3H] galactose-containing fractions from CsCl density gradients of culture supernatants or macrophage lysates were capable of clotting Limulus amebocyte lysate. The [3H]galactose material obtained from 48-hr macrophage lysates and culture supernatants could also induce a lethal response in actinomycin D-treated mice. These data suggest that bacterial LPS may be selectively retained by the macrophage and that the post-phagocytic events that result in bacterial degradation are not accompanied by the degradation of LPS. Furthermore, although the LPS may be modified by the macrophage, it retains its biologic activity.

Animals↗
PubMed1983

Immune responses to hapten-lipopolysaccharide conjugates in mice. III. Genetics of the antibody response to polysaccharide antigens.

Antibody responses to the polysaccharide antigens of bacterial lipopolysaccharides and their hapten derivatives are herein documented to be under multigenic control. Among the genes responsible for the antibody response to these polysaccharide antigens include those coded for by genes located on the X chromosome and those on chromosome 17 linked to genes in the H-2 and/or Qa loci. The use of B10 congenic mice revealed that two genes on chromosome 17 are involved in the regulation of the antibody response to bacterial polysaccharide antigens. The use of CXB recombinant inbred mice confirmed the multigenic control of the antibody response within their background array of genes. The data clearly demonstrate that immune responses to these polysaccharide antigens are under genetic control, the importance of which may be of significance with regard to humoral protection during gram-negative infection.

Animals↗
PubMed1983

Conversion of lipopolysaccharides to molecular aggregates with reduced subunit heterogeneity: demonstration of LPS-responsiveness in "endotoxin-unresponsive" C3H/HeJ splenocytes.

Lipopolysaccharides (LPS) of homogeneous monomeric composition were prepared by gel filtration chromatography of detergent-dissociated LPS from the smooth strain of E. coli 055:B5. Splenocyte mitogenic activity of reassociated column fractions and fraction pools is markedly dependent upon the ratio of O-antigen polysaccharide to lipid A. The activity of the homogeneous LPS in eliciting spleen cell responses varied by approximately three orders of magnitude. One of the fraction pools rich in lipid A (which contains only a trace of O-antigen polysaccharide) induces a spleen cell proliferative response in C3H/HeJ "LPS-nonresponder" spleen cells. This mitogenic activity is not present in either unfractionated LPS or O-antigen-rich fractions. These latter findings indicate LPS macromolecular aggregates of the appropriate physicochemical structure have the capacity to elicit C3H/HeJ spleen cell proliferative responses.

Animals↗
PubMed1983

Interaction of latex-insolubilized endotoxins with murine macrophages: phagocytic responses of endotoxin-responsive (C3HeB/FeJ) and -unresponsive (C3H/HeJ) macrophages in vitro.

Insolubilized lipopolysaccharides (LPS) were prepared by covalently coupling LPS from polysaccharide-deficient S. minnesota R595 and polysaccharide-rich E. coli 055:B5 to carboxylated latex particles. The stability of these LPS-latex complexes was determined using several assays to detect soluble LPS following incubation at ambient and elevated temperatures. Resident and thioglycollate-elicited macrophages from both LPS-responder C3HeB/FeJ and LPS nonresponder C3H/HeJ mice were examined for their capacity to phagocytose the LPS particles following in vitro culture for various time periods. Uptake was demonstrated by an increase in the number of particles within the macrophages with increasing time of incubation. Rough polysaccharide-deficient LPS-latex particles were found to be more readily phagocytosed than control particles, whereas smooth polysaccharide-rich LPS particles were phagocytosed less readily than the controls. Qualitatively similar results were found in the relative rate of uptake of particles by the macrophages from the endotoxin-responsive and -unresponsive mouse strains used in this study.

Animals↗
PubMed1982

Possible alteration of normal mechanisms of endotoxin toxicity in vivo by actinomycin D.

The effect of actinomycin D on the sensitivity of endotoxin-responsive (C3HeB/FeJ) and endotoxin-unresponsive (C3H/HeJ) mice to challenge with purified lipopolysaccharide (LPS) of Escherichia coli strain O55:B5 was examined using an experimental protocol of adoptive transfer of lymphoid cells into lethally irradiated recipients. Earlier results--that in the absence of actinomycin D, the ability of LPS to cause a lethal response in the immunologically chimeric mice reflected the phenotypic response of the donor lymphoid cells--were confirmed. Simultaneous administration of actinomycin D to endotoxin-responsive C3HeB/FeJ mice increased by several orders of magnitude the sensitivity of these mice to the lethal effects of LPS. Determinations of 50% lethal doses in the presence of actinomycin D indicated that immunologic chimeras were sensitive to lethal effects of LPS if either the donor or the recipient phenotype was LPS-responsive. Thus, the mechanism(s) of host response to LPS in the presence of actinomycin D may not be identical to those elicited in untreated mice.

Animals↗
PubMed1982

Evidence for different requirements in physical state for the interaction of lipopolysaccharides with the classical and alternative pathways of complement.

The influence of the state of aggregation of lipopolysaccharides upon their ability to interact with serum complement via either the classical or alternative pathway was studied. The anticomplement properties of two chromatographically distinct fractions of a phenol-extracted lipopolysaccharide isolated from Serratia marcescens were assessed by means of the standard sheep erythrocyte hemolytic assay and an alternative pathway-selective kinetic assay using rabbit erythrocytes. Both the high molecular weight PI fraction and the lower molecular weight PII fraction exerted anti-complement activity as determined in the sheep erythrocyte assay. Conversion of fractions PI and PII to their more soluble triethylamine salt forms resulted in a decrease in sedimentation coefficients and a corresponding loss of anticomplement activity. Further, the anticomplement activity of fractions PI and PII in the sheep erythrocyte assay was inhibited by polymyxin B, indicating a role for the lipid A region. Unlike the PII fraction, only the PI fraction can activate serum complement via the alternative pathway. This activity is not inhibited by polymyxin B, indicating that the response is not lipid A-mediated. Significantly, solubilization of the PI fraction with triethylamine had no effect on its ability to activate the alternative pathway. These studies clearly demonstrate that the interaction between lipopolysaccharides and serum complement is influenced by the state of lipopolysaccharide aggregation. However, this appears to be the case for lipopolysaccharide activation of the classical pathway but not of the alternative pathway.

Adult↗
PubMed1982

Prolonged suppression of experimental allergic encephalomyelitis in the Lewis rats: the effect of lipopolysaccharides.

The current investigations have revealed that Lewis rats preimmunized with BP in CFA, and after recovery from the first episode of EAE, developed a second mild attack of EAE after challenge with BP/CFA at specified times. However, preimmunization of Lewis rats with BP complexed to LPS in CFA protects animals for a longer time from a second attack induced by BP/CFA challenge.

Animals↗