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M LANDY

Publications and source records attributed to M LANDY.

At least 55 records · Page 3Linked to original sources

Inactivation of endotoxin by a humoral component. II. Interaction of endotoxin with serum and plasma.

A humoral substance which inactivates endotoxin in vitro has been shown to be clearly distinguishable from complement, properdin, and specific antibody. For the present, it is designated "endotoxin-detoxifying component" or EDC. Animal species could be grouped in three categories with regard to the EDC activity of their sera; rat serum was highly potent; chimpanzee, dog, horse, and guinea pig sera were much less active; mouse, rabbit, and sheep sera exhibited no activity. The EDC potency of human sera varied widely, ranging from high to barely discernible activity. In contrast to the variations of EDC potency in serum, citrated plasma from all species manifested high potency of about the same magnitude. The influence of time, temperature, pH, and concentration of reactants on the inactivation of endotoxin by EDC was examined. EDC activity in plasma and serum was found to be labile to beating at 56 degrees C. for 1 hour. Bacterial endotoxins, derived by different isolation procedures from smooth and rough Gram-negative species, varied considerably in susceptibility to EDC action.

Animals↗

Inactivation of endotoxin by a humoral component. III. Role of divalent cation and a dialyzable component.

The uniformly high potency of citrated plasma as compared with the limited capacity of serum to inactivate endotoxin in vitro was found to be a consequence of the anticoagulant employed in collecting the plasma. Addition of calcium to plasma suppressed the activity of its endotoxm detoxifying component (EDC) whereas the addition of calcium-binding anticoagulants rendered serum comparable to plasma. Dialysis of plasma resulted in a marked reduction of its EDC activity despite the concommittant elimination of calcium. EDC activity could then be fully restored upon the addition of calcium-binding anticoagulants. Resin-treated plasma, without added anticoagulant, had EDC activity equal to plasma obtained with calcium-binding anticoagulants. Following dialysis, resin-treated plasma also sustained a marked reduction in EDC activity which could be fully restored by calcium-binding anticoagulants. Restoration was also obtained with the dialysate even after ashing. These findings indicated that the suppression of EDC activity by calcium is not direct but is mediated through its effects on an anionic component of plasma which is required for inactivation of endotoxin by EDC.

Bacteria↗

Similarity of host responses elicited by polysaccharides of animal and plant origin and by bacterial endotoxins.

Ten polysaccharides, isolated from various animal and plant sources, were selected for comparison with 2 bacterial polysaccharides, typical of Gram-negative endotoxins. The tissue sources were: mouse (kidney, liver, lung, stomach, Sarcoma 37, and Carcinoma 241-6); rabbit skin and chick embryo skin; and tangerine and Bryonia root. The bacterial endotoxins were those of S. typhosa and Serr. marcescens. Their relative potency was determined in inducing the following host effects: fever, tolerance to pyrogenic action, leucocytic changes, the Shwartzman reaction, damage to Sarcoma 37, dermal hemorrhagic-necrosis by epinephrine, enhancement of antibody production, and lethality. Some of the polysaccharides were consistently active in all the host reactions studied; except for pyrogenic activity at high dosage, the other polysaccharides were consistently negative throughout. The mouse tissue polysaccharides elicited all the effects studied; in some instances their potency approached those of the bacterial polysaccharides. It is pointed out that elicitation of the above array of biological phenomena, hitherto considered characteristic of bacterial endotoxins, can be obtained with polysaccharides from animal and plant tissues.

Animals↗

The properdin system and immunity. VII. Alterations in properdin levels and resistance to infection in mice following the administration of tissue polysaccharides.

High molecular weight polysaccharide complexes derived from normal and neoplastic mammalian tissues were found to combine with properdin and to inactivate C'3 in vitro. These polysaccharide preparations were also found to alter properdin levels and non-specific resistance to Gram-negative infection in mice. In these manifestations, the tissue polysaccharides bore a marked resemblance to bacterial lipopolysaccharides. Some implications of the interactions of tissue polysaccharides and properdin in certain disease states are considered.

Animals↗

Increased resistance to infection and accompanying alteration in properidin levels following administration of bacterial lipopolysaccharides.

It has been shown that injection of lipopolysaccharides, derived from a variety of Gram-negative bacterial species, evokes in mice a rapidly developing rise in resistance to infection with Gram-negative pathogens. This is accompanied by an elevation in properdin titer, at times to levels 2 to 3 times the normal. The rate, magnitude, and duration of these responses are dependent on many factors, the most important of which are the quantity and timing of the lipopolysaccharide administered. The increased resistance to infection evoked in mice by lipopolysaccharides was effective against infections produced by endotoxin-bearing organisms-bacterial species highly susceptible in vitro to the bactericidal action of the properdin system. Properdin titers of mice prior to infection provide an incomplete picture of the subsequent reaction of the host to the infective agent. Following infection with Gram-negative organisms, properdin levels accurately reflect the bacteriologic course and outcome of the infection. Thus, in control animals, properdin titers progressively declined and the animals died, while in mice appropriately treated with lipopolysaccharide, properdin levels were either maintained in the normal range or increased, depending on the dose and time of administration of lipopolysaccharide; this was always accompanied by successful management of the infection. The complex nature of the alterations produced in the host by lipopolysaccharides is stressed. It is pointed out that the increase in the ability of the host to cope with Gram-negative infections may be the result of stimulation of other defense mechanisms, in addition to the properdin system.

Animals↗

Elevation of properdin levels in mice following administration of bacterial lipopolysaccharides.

The administration of a single small dose of bacterial lipopolysaccharide produces in mice a considerable rise in properdin levels. This is accompanied by an early, transient, non-specific increase in resistance to certain bacterial infections. Bacterial lipopolysaccharides were shown to possess far greater activity than other substances previously studied in bringing about an elevation of properdin levels. After the injection of bacterial lipopolysaccharides, high molecular weight substances appear in the circulation, which interfere with the combination of properdin with zymosan and thus affect the assay of properdin. The administration of small amounts of bacterial lipopolysaccharides to mice at appropriate times before experimental infection "conditions" the mice so that they maintain normal or elevated properdin titers during the infectious process in contrast to control mice which show a progressive decline in properdin to low levels and death. The significance of this observation and its relationship to natural resistance to Gram-negative pathogens are considered.

Animals↗

Studies on the O antigen of Salmonella typhosa. V. Enhancement of antibody response to protein antigens by the purified lipopolysaccharide.

Quantitative studies have demonstrated that a purified lipopolysaccharide (endotoxin) derived from the O-901 strain of Salmonella typhosa markedly enhanced the antibody response of rabbits when given separately or in conjunction with protein antigens. The augmentation of antibody levels varied from 2- to 40-fold with the number of injections, the dosage of antigen and endotoxin, and the route of administration. This antibody-enhancing property was found to be common to a broad group of endotoxins from Gram-negative bacilli and was not restricted to the lipopolysaccharide derived from S. typhosa. Factors affecting this enhancement were investigated, and data are presented which indicate that host susceptibility to endotoxin is a prerequisite for elevation of antibody levels; the intact lipopolysaccharide, as isolated, might not be essential for this activity; and the rate of clearance of antigen from the circulation of rabbits was accelerated when endotoxin was given in conjunction with protein. The data obtained are discussed in relation to postulated mechanisms on the antibody-enhancing action of endotoxin.

Animals↗