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D C Morrison

Publications and source records attributed to D C Morrison.

At least 145 records · Page 8Linked to original sources
PubMed1982

Immunosuppression of experimental allergic encephalomyelitis. III. In vitro evidence for induction of suppressor T lymphocytes in draining lymph node cells of animals immunized with myelin basic protein complexed to lipopolysaccharides.

We recently demonstrated that Lewis rats immunized with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP) in complete Freund's adjuvant were less effective in inducing experimental allergic encephalomyelitis (EAE) than BP-immunized controls. When tested in vitro both lymph node cells (LNC) and spleen cells (SpC) of animals immunized with BP-LPS were less effective in proliferative responses to various mitogens, which included phytohemagglutinin, concanavalin A, purified protein derivative of tuberculin, LPS, and BP. Of importance immunization of rats with BP complexed to LPS results in the generation of cells in lymph nodes of these animals that suppress the mitogenic response of BP-immunized LNC and also SpC in mixed lymphocyte cultures. The suppressive effect of these cells in mixed lymphocyte culture reaction was found specifically in response to BP and to a lesser extent to LPS in LNC. SpC of BP-LPS immunized animals did not suppress the proliferative response to SpC of BP-immunized animals. Treatment of these LNC with antithymocyte serum and complement abolished this suppressive effect of LNC, suggesting that the immunoregulatory cells in LNC of BP-LPS immunized animals are suppressor T lymphocytes. The parallel between the in vitro induction of suppressor T lymphocytes in the draining LNC and the function of LPS in the development of EAE in Lewis rats suggests a possible immunologic significance of the effect.

Animals↗
PubMed1981

Binding of bacterial endotoxin (LPS) to encephalitogenic myelin basic protein and modulation of characteristic biologic activities of LPS.

Myelin basic protein, isolated from central nervous system tissue and an inducer of experimental allergic encephalomyelitis in animals, has been demonstrated to form a stable molecular complex with the lipid A region of gram-negative bacterial lipopolysaccharides (endotoxins). This binding of endotoxin with myelin basic protein results in generation of lower m.w. aggregates with decreased isopycnic density. A number of lipid A-induced characteristic properties of endotoxin, such as B lymphocyte proliferative response in C3H/St mice, complement activation of normal human serum, Limulus lysate gelation, and lethal effects in mice, are modified as a result of binding of myelin basic protein with lipopolysaccharides.

Animals↗
PubMed1981

Prevention of experimental allergic encephalomyelitis by bacterial lipopolysaccharides: inhibition of cell-mediated immunity.

The immunization of Lewis rats with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP) in complete Freund's adjuvant inhibits the development of experimental allergic encephalomyelitis (EAE) in these animals. These protected animals fail to manifest significant in vivo delayed-type hypersensitivity skin tests and in vitro lymphocyte proliferative responses to BP. Our results indicated that LPS induces a nonspecific reduction in immune reactivity of BP in Lewis rats.

Animals↗
PubMed1981

Experimental allergic encephalomyelitis in Lewis rats: inhibition by bacterial lipopolysaccharides and acquired resistance to reinduction by challenge with myelin basic protein.

In 2-mo-old Lewis rats immunized with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP), the clinical and histologic manifestations of experimental allergic encephalomyelitis (EAE) were diminished compared with BP-treated controls. Similarly, in animals immunized with BP and challenged with BP-LPS at the same time or as long as 5 days after, the immunization with BP also inhibited the disease. That this capacity to reduce the incidence of BP-induced EAE is a unique property of LPS was suggested by the fact that other negatively charged molecules, such as DNA, RNA, and dextran sulphate, were not effective in inhibiting the clinical signs of EAE. After recovery from EAE induced by BP, some animals develop a recurrence of the disease if challenged with BP at appropriate intervals. However, after recovery from mild EAE induced by BP-LPS and after challenges with EAE-initiating BP antigens, secondary EAE was inhibited significantly.

Animals↗
PubMed1981

Hemopoietic effects in mice of a lipid A-associated protein.

The effects of the bacterial cell-wall components (BCWC) lipid A and lipid A-associated protein (LAP) on humoral and cellular hemopoietic parameters were investigated in mice. Both lipid A and LAP increased serum levels of granulocyte-macrophage colony-stimulating factors (CSF) in C57BL/6 mice. In C3H/HeJ mice the CSF responses to lipid A and LAP were 7 and 3 fold less than the corresponding CSF responses found in C3H/GSF mice. Both BCWC increased the numbers of splenic multipotential hemopoietic stem cells (CFUS) as well as colony-forming cells (CFC) for neutrophilic granulocytes, macrophages, eosinophils and megakaryocytes. Lipid A but not LAP caused a marked decrease in the femoral numbers of B lymphocyte colony-forming cells (BL-CFC). The Bl-CFC incidence in the spleen or in the mesenteric lymph node changed little if at all after injection of either of the two BCWC. Morphological analysis of marrow cells showed an increase in the proportion of myeloid cells and a concomitant decrease in the proportion of erythroid precursor cells after injection of both BCWC. In the spleen, lipid A but not LAP caused an increase in the proportion of myeloid cells, erythroid precursor cells and plasma cells. In all experiments where both BCWC showed activity, lipid A was more potent than LAP on a weight basis.

Animals↗
PubMed1981

Biochemical mechanisms of lipid-A-mediated enhancement of platelet secretory responses to aggregated immunoglobulins.

The mechanism by which endotoxins enhance the secretory response of washed preparations of human platelets to aggregated immunoglobulins (Agg-HGG) has been examined. Preparations of endotoxins from several rough mutants of bacteria enhance, by approximately 50-fold, the release of serotonin initiated by Agg-HGG. Endotoxins from smooth strains do not manifest this enhancement, and all endotoxin preparations are completely inactive in the absence of Agg-HGG. Preincubation and wash experiments have demonstrated that the critical initial interaction is the formation of complexes between the endotoxin and the Agg-HGG stimulus and is not dependent on an initial endotoxin-platelet interaction. Pretreatment of platelets with substimulatory concentrations of Agg-HGG, followed by the addition of endotoxin, causes a temporal decay in the degree of endotoxin-induced enhancement, which is inversely related to the concentration of Agg-HGG. This stimulus-specific desensitization suggests that the endotoxin-Agg-HGG complexes initiate release by a pathway similar to that initiated by Agg-HGG alone. We postulate that the endotoxin either enhances or stabilizes a localized platelet membrane perturbation or deformation, initiated by the Agg-HGG stimulus.

Blood Platelets↗
PubMed1980

Lipid A dependence of the ocular response to circulating endotoxin in rabbits.

The effects of bacterial lipopolysaccharides on ocular vascular permeability were measured after their intravenous injection in rabbits. Alterations in ocular vascular permeability were quantitated by the accumulation of 125I-labeled albumin in the enucleated eye compared with that in heart blood (ocular albumin space). Two lipopolysaccharides extracted from Escherichia coli O111:B4, one with high lipid A content and one with high polysaccharide content, were tested initially, and the one with greater lipid A was 200 times more effective in producing an alteration in ocular vascular permeability. Lipopolysaccharide from a rough strain, Salmonella minnesota (R595), containing lipid A primarily, as well as a purified lipid A extracted from +595, were also effective. But an extract of the protein associated with lipid A was without significant effect. In vitro pretreatment of the lipopolysaccharides with polymyxin B, an inhibitor of the biological activity of lipid A through direct binding, could abrogate the ocular response. These results indicate the paramount importance of the lipid A moiety in the ocular response to circulating endotoxin.

Animals↗
PubMed1980

An in vitro line of the B cell tumor BCL1 can be activated by LPS to secrete IgM1.

An in vitro line of the B cell tumor BCL1 was developed. The cell line carried u-, S-, and A-chains on the cell surface as judged by analysis of surface iodinated proteins but did not secret Ig. ASfter stimulation with LPS, limpid A, or bacterial lipoprotein, 20 to 40% of the tumor cells matured to IgM secretors when detected in a plaque assay. Two other polyclonal B cell activators, namely dextransulphate and PPD, had at most a marginal stimulatory effect. The ability of the cells to become activated to IgM secretion as well as the expression of cell surface IgM and IgD makes the BCL1 unique among murine B cell tumors.

Animals↗
PubMed1980

Stimulation of peritoneal cell arginase by bacterial lipopolysaccharides.

The conditions under which bacterial endotoxins stimulate arginase production in mouse peritoneal macrophages have been defined. Both lipid-A and lipid-A-associated protein are potent activators. Fetal calf serum and normal mouse serum enhance macrophage arginase levels in the presence and absence of lipopolysaccharide (LPS). LPS in the amount of 10(-1) microgram/ml represents a maximal stimulus for macrophage arginase production and release. Thioglycollate-elicited peritoneal cells have increased arginase activity, compared with resident cells. This activity can be stimulated further by the addition of LPS. Arginase levels may alter the outcome of in vitro immunologic processes by depleting arginine and may also serve as a useful indicator of the state of activation of macrophages.

Animals↗
PubMed1980

Effect of lipid A-associated protein and lipid A on the expression of lipopolysaccharide activity. I. Immunological activity.

A detailed investigation has been made of the contribution of the various chemical moieties of bacterial endotoxins, namely lipid A-associated protein (LAP), lipid A and O-antigen polysaccharide to a number of the immunological activities of these active bacterial products. Advantage was taken of the availability of antigenically identical endotoxin preparations from Escherichia coli 0111:B4 which differed greatly in their content of LAP and/or lipid A. The capacity to initiate in vitro proliferative responses in murine splenocytes was in a large part related to the presence of LAP with a less potent, although still critical, dependence upon lipid A. On the other hand, the in vivo polyclonal antibody response was dependent only upon lipid A. In this respect, the presence of LAP had no apparent effect on the stimulation of nonspecific low affinity antibody. All preparations, regardless of LAP and lipid A content, stimulated similar in vivo enhancement of antibody responses to a protein antigen (adjuvanticity) and specific immune responses to the endotoxin polysaccharide antigen. The results emphasize the lack of correlation between in vitro B lymphocyte proliferative responses and in vivo immunostimulatory responses of bacterial endotoxin preparations. These data also suggest a minimal contribution of LAP to in vivo responses and an extremely limited contribution of lipid A to the adjuvant activity and the primary immune response to O-antigen polysaccharide.

Adjuvants, Immunologic↗