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Biomedical subjects

J J Pruzansky

Publications and source records attributed to J J Pruzansky.

At least 19 recordsLinked to original sources
PubMed1989

IgG antibody against formaldehyde human serum proteins: a comparison with other IgG antibodies against inhalant proteins and reactive chemicals.

Immune responses to formaldehyde (F) have been recorded for seven decades. More recently, sensitive assays for antibody against F-human serum albumin (HSA) have been reported. IgG antibody against F-HSA has been said to correlate with symptoms against F-HSA. We report on 61 serum samples analyzed for IgG antibodies against F-HSA. IgG antibodies against F-HSA were most prevalent in subjects who had received intravenous F. In no case (either presumed symptomatic to F or with IgG antibody against F-HSA) was there a correlation of serologic results with symptoms. We also reviewed inhalation disease caused by chemicals and proteins acting as immunogens and report that at this time there is no evidence that gaseous F meets the criteria for causation of inhalational IgG-mediated lung disease by clinical or serologic studies. Very high IgG antibody levels occur in respiratory immunologic inhalational disease, and the absence of these high IgG levels against F is strong evidence against F or F proteins being an inhalational antigen of significance.

Allergens↗
PubMed1988

The laboratory evaluation of IgE antibody to metabisulfites in patients skin test positive to metabisulfites.

An immediate-type hypersensitivity reaction has been proposed as one possible mechanism in which metabisulfites (MBSs) cause reactions. As demonstrated with certain occupational chemicals, we proposed that MBS might conjugate with human proteins, such as human serum albumin, and then cause an immunologic response. Because we had identified no reactions to MBS at the Northwestern Allergy Service, we used sera from four patients reported elsewhere as having positive skin tests and positive oral challenges to sulfites. We attempted to demonstrate, both in vitro by ELISA and in vivo by passive cutaneous transfer to monkey, evidence for IgE-mediated hypersensitivity to MBSs. Our results demonstrated that there is evidence of IgE antibody by passive transfer for one patient studied, but no evidence of IgE antibody by ELISA to an MBS-albumin conjugate in any of the four patients. This study illustrates the complexities involved in the evaluation and mechanism of MBS-induced disease and the caution with which results must be interpreted.

Animals↗
PubMed1988

Evidence for in vitro regulation of IgE receptors on the human basophil membrane by their removal and reexpression: effects of Ca2+, Mg2+, some metabolic inhibitors and fetal calf serum.

Human basophils free of receptor-bound IgE and suspended in RPMI-1640 + 0.2% EDTA or in a buffered salt solution lacking Ca2+ and Mg2+ bound optimal quantities of 125I IgE. In media containing Ca2+ and Mg2+ such as RPMI-1640 alone or a buffered physiologic salt solution binding was reduced significantly in the first 60 min and remained essentially unchanged in the next 120 min. Scatchard analysis showed the reduction to be due both to loss of number and affinity of receptors. The presence of both 2-deoxy-d-glucose and 2,4-dinitrophenol usually prevented the reduction of binding in RPMI-1640. Suspension of cells in RPMI-1640 supplemented with fetal calf serum (FCS) demonstrated reduction in binding at 60 min characteristic of divalent-cation-containing media but this was followed by a rise in binding to approximately control levels in the next 120 min. This pattern of binding occurred in about 70% of the experiments. In most of the remaining experiments there was no difference from control binding in that there was no early decrease and no late rise in binding. This variability was not leukocyte-donor-dependent. When cells were preloaded with 125I IgE and incubated in RPMI-1640 dissociation of IgE was more rapid than in media free of Ca2+ and Mg2+. The results suggest that membrane-bound IgE receptors on basophils may be shed by an energy and Ca2+ and Mg2+ requiring process and reexpressed dependent on a factor or factors present in FCS.

2,4-Dinitrophenol↗
PubMed1988

Desensitization of human basophils with suboptimal concentrations of agonist. Evidence for reversible and irreversible desensitization.

Leucocytes from allergic donors were preincubated with suboptimal concentrations of ragweed or anti-IgE and then challenged with increasing concentrations of the homologous or heterologous agonist. The initial incubation resulted in desensitization, as judged by a reduced reactivity relative to controls preincubated without agonist but challenged similarly. Both homologous and heterologous desensitization were observed and were dose dependent. Evidence was obtained for both a reversible and irreversible component of desensitization, which was also agonist-concentration related. Reversibility occurred to a similar degree either by incubation of suboptimally desensitized cells with optimal concentrations of agonist or by removal of IgE and resensitization. This could implicate IgE-agonist aggregation on the basophil surface as a mechanism of desensitization. Histamine release from desensitized cells was highly correlated with degranulation, suggesting that individual cells were desensitized in an all-or-none manner.

Antibodies, Anti-Idiotypic↗
PubMed1988

Limiting concentrations of human basophil-bound IgE antibody required for histamine release.

Human blood basophils were treated to remove resident IgE, and passively sensitized with mixtures of ragweed antigen E-specific and non-specific IgE under receptor-saturating conditions. At a ratio of about 0.005 (0.5%) specific IgE or higher, maximal histamine release was observed, but below this a progressive decrease occurred. With leucocytes of four donors, minimal ratios producing mediator release above background varied from 0.001 to 0.00034, which was roughly inversely related to the number of IgE receptors per basophil. This indicated that for these donors' cells a similar number of specific IgE molecules was required for histamine release, and calculation showed the numbers to be 30-55, despite a five-fold difference in total numbers of IgE receptors between different donor basophils. Therefore, it could be estimated that the minimal number of bridges required for basophil activation was to the order of 10-15, depending on whether divalent or trivalent bridges were involved. Since percentage histamine release and percentage degranulated cells were highly correlated after suboptimal sensitization, individual cells or subsets of basophils were apparently differentially responsive. This is consistent with other evidence of functional heterogeneity and that histamine release by individual cells is an all or none process.

Allergens↗
PubMed1986

Binding constants of IgE receptors on human blood basophils for IgE.

The ability to remove receptor-bound IgE but maintain functional integrity of human blood basophils allowed measurement of several parameters of binding of IgE. Non-specific binding was determined by a modification of the standard technique and was found to be only about 10% of specific binding. The number of free receptors varied inversely with the serum IgE of the donor. Forward rate constants were readily measured at 0 degree but were considerably higher at 37 degrees, and a rough estimate of the activation energy for binding was calculated to be 6700 calories/mol. Saturation of basophil receptors with IgE occurred in 1-3 h using 3.6 micrograms 125I-IgE/ml at 37 degrees. For seven donors, the forward rate constant, k1, ranged from 2.9 to 7.25 X 10(4) M/sec with a mean of 5.2 X 10(4)/M/sec. This is about one-third the reported value for cultured cord blood basophils. The backward rate constant, k-1, ranged from 1.4 to 3.9 X 10(-5)/sec with a mean of 2.5 X 10(-5)/sec. This is less than half that of cord blood basophils. The equilibrium association constant, Ka, ranged from 1.4 to 2.7 X 10(9)/M with a mean of 2.1 X 10(9)/M. This is comparable to the high affinity binding reported for cord blood and other basophils. There was no great difference in binding constants among the four atopic and three non-atopic donors studied. The affinity of monoclonal mouse 125I-IgE for IgE receptors on human basophils was about four-fold lower than that of human IgE. Sensitization of human basophils for histamine release with mouse IgE anti-DNP was confirmed. Non-specific human IgE but not IgG inhibited sensitization by mouse IgE, indicating that the same receptors were involved and that they were specific for IgE.

Basophils↗
PubMed1984

Hapten-modified basophils: a model of human immediate hypersensitivity that can be elicited by IgG antibody.

Trimellitic anhydride (TMA) was incubated with human leukocytes to produce leukocytes with trimellityl (TM) haptenic determinants. The basophils in these TM leukocytes released histamine when challenged with human serum containing IgG but no IgE antibodies against TM determinants. Controls of TMA-treated cells exposed to normal human sera or untreated cells exposed to anti-TM sera released no histamine. The most relevant site of TMA modification of the basophil was receptor-bound IgE. This was demonstrated by the marked reduction in histamine release if IgE was removed from the leukocytes before TMA treatment and challenge and also by activation of release from untreated cells by passive sensitization with TM-IgE before challenge. Affinity-purified IgG from an anti-TM serum released much more histamine from TMA-treated cells than did the IgG-poor effluent at similar protein concentrations. These observations suggest a new model of hypersensitivity resulting from human exposure to chemicals capable of combining with autologous proteins. In some individuals this could result in both an immune response to the new determinants without the production of significant quantities of IgE antibodies and hapten modification of receptor-bound IgE on mast cells and basophils. After sufficient antibody was produced, reexposure to the chemical with hapten modification of mast cells or basophils or both could result in mediator release and clinical symptoms. This mechanism may be relevant to immediate-type chemical hypersensitivity reactions in which IgE antibody has not been demonstrated.

Basophils↗
PubMed1984

Neutrophil chemotactic activity released in supernatants of human leukocytes challenged with antigens or anti-human IgE.

Neutrophil chemotactic activity was released into the supernatants of leukocytes from atopic individuals challenged with rabbit anti-human IgE, ragweed, or Aspergillus fumigatus antigen and from nonatopic individuals only on challenge with anti-IgE. Using a recently reported procedure for removing IgE from basophil receptors, it was possible to passively sensitize leukocytes from nonatopic individuals with plasma from atopic donors and to convert nonreleaser cells to cells releasing neutrophil chemotactic activity specifically. Histamine release measured in the same supernatants of immunologically challenged cells correlated with neutrophil chemotactic activity release, consistent with the interpretation that basophils and IgE mediation are involved in this phenomenon. The neutrophil chemotactic activity was not caused by histamine released from basophils. Activity persisted after incubation at 56 degrees C for 30 minutes. Chemokinetic activity was also present in the supernatants, because migration was not inhibited completely in the absence of a gradient.

Animals↗
PubMed1983

A solid-phase bead radioimmunoassay for specific IgE to ragweed antigen E.

A solid-phase bead radioimmunoassay has been developed for measuring IgE against antigen E (IgE-a-AgE) in serum. The patient's IgE is bound by monoclonal mouse anti-human IgE which is on the surface of a solid bead. Other immunoglobulin classes are not bound and can be washed away. Radiolabeled AgE is then added and is specifically bound by IgE-a-AgE. This assay is reproducible, and in contrast to specific IgE assays utilizing RAST methodology, it cannot be inhibited by specific antibody of other classes. Moreover, the solid-phase bead method does not utilize myeloma IgE. Finally, its results correlate well with those of a previously developed polystyrene tube method.

Allergens↗
PubMed1983

Hyperreactivity of mediator-releasing cells from patients with allergic bronchopulmonary aspergillosis as evidenced by basophil histamine release.

Histamine release was performed on 28 patients with allergic bronchopulmonary aspergillosis (ABPA) in various stages and on 14 patients with mold-sensitive asthma, by using Aspergillus antigens, other mold antigens, and anti-IgE. Total serum IgE, IgE and IgG antibodies to Aspergillus fumigatus (Af), and end point cutaneous titration for Af were determined for each patient. There was greater histamine release to Aspergillus mix (p = 0.0000) and anti-IgE (p = 0.047) in patients with ABPA than in patients with mold-sensitive asthma. Patients with stages IV and V ABPA had greater histamine release to Aspergillus mix than patients with stage I, II, or III ABPA (p = 0.0014). There was greater histamine release to other molds in ABPA patients than in mold-sensitive asthmatics. There was no correlation between histamine release to Aspergillus mix and total serum IgE, IgE or IgG antibodies to Af, ratio of IgE and IgG antibodies to Af to total IgE, or cutaneous end point titration for Af in ABPA patients or mold-sensitive asthmatics. Peripheral basophils from ABPA patients demonstrated marked hyperreactivity as evidenced by histamine release to Aspergillus antigens, other molds, and anti-IgE. This hyperreactivity is the first cellular difference recognized in ABPA patients when compared to mold-sensitive asthma patients. If this hyperreactivity is manifested by mediator release from other cells such as pulmonary mast cells, which would be in close contact with growing Af, a possible mechanism for pulmonary response in ABPA would be suggested.

Adolescent↗
PubMed1983

Induction of IgE-mediated cutaneous, cellular, and airway reactivity in rhesus monkeys by Ascaris suum infection.

In order to maintain a colony of rhesus monkeys with IgE-mediated Ascaris asthma, we evaluated the response of four animals to infection with Ascaris suum ova. All four animals developed immediate-type cutaneous reactivity and airway responses. Serum IgE and IgG antibody responses against Ascaris antigen, as quantitated by the ELISA, were seen in all animals. Peripheral blood histamine release after stimulation with Ascaris antigen was positive in all animals. Airway reactivity to aerosol challenge with Ascaris antigen became positive in all animals and has remained positive for 6 months in three of four animals. Both standard and threshold dose airway types of responses were present. Except for transient eosinophilia, the animals remained in good health. The studies demonstrate that infection with A. suum results in rhesus monkeys with IgE-mediated immediate-type reactivity that simulates the naturally occurring model of asthma.

Animals↗
PubMed1983

Dissociation of IgE from receptors on human basophils. I. Enhanced passive sensitization for histamine release.

Leukocytes of only one of 11 nonatopic donors could be passively sensitized for histamine release elicited by ragweed extract. A short incubation in an unbuffered isotonic saline at pH 3.9 or in an 0.01 M lactic acid/lactate-buffered isotonic saline at pH 3.9 dissociated from 4 X 10(5) to less than 3 X 10(4) IgE molecules per basophil from washed leukocytes of several in a series of six atopic and 11 nonatopic donors. After such treatment, leukocytes of only one of the 11 nonatopic donors could not be sensitized for histamine release. Basophils of the four ragweed-sensitive donors lost their sensitivity to ragweed after the treatment, but all could be passively resensitized; for three of these donors the level of release approximated their original reactivity. Leukocytes of the two mold-sensitive donors could be passively sensitized to ragweed allergens after but not before treatment. Four plasma samples from histamine release-positive volunteers were used for sensitization of treated leukocytes of each cell donor; three were consistently effective and one was consistently ineffective. The positive plasmas had concentrations of antigen E-specific IgE of over 100 ng/ml, which accounted for 17 to 23% of the total IgE; the inactive one had less than 5 ng/ml of specific IgE. For each cell donor, all three samples of active plasma mediated quite similar histamine release, but there was a spectrum of donor cell reactivity ranging from 23 to 70% release. These results suggest that basophils from each donor, atopic or nonatopic, had a maximal potential for in vitro sensitization, which was only attained if the plasma contained appropriate, but yet to be fully defined, concentrations of specific and total IgE. Several unexpected results were obtained. Treated leukocytes from some individuals were sensitized for mediator release to a greater extent by sixfold diluted than undiluted plasma. In addition, a 4-hr incubation with plasma at 37 degrees C, but not at 25 degrees C or 0 degrees C, was less effective than were shorter incubation periods. Treated leukocytes should be useful in studying kinetic and equilibrium parameters of IgE binding to specific receptors on human basophils. Analogous treatments should also be useful in sensitization and measurement of IgE-receptor interactions of mast cell populations.

Basophils↗
PubMed1982

Quantification of ultrastructural variations in enriched blood basophils: correlation of morphological changes and antigen-induced histamine release.

Highly purified preparations of human basophils have been studied ultrastructurally to delineate quantifiably those alterations associated with immunologically-induced histamine release. Of six characteristic variations of basophil morphology, totally degranulated cells, those with some exteriorized granules and those with some extracellular vesicles were almost exclusively associated with antigen challenge. Of these, total degranulation without extracellular granules or vesicles was most frequent. A correlation was found between percentage histamine released and percentage totally degranulated cells present in the samples incubated with antigen. In addition, increased plasma membrane folding and irregularity were more prevalent in stimulated samples than in controls and their mean frequency was related quantifiably to the percentage of histamine released in each group. Cells with empty vesicles or electronlucent intracellular granules or both occurred to the same extent in experimental and control aliquots. The possible of histamine release is discussed.

Antigens, Fungal↗
PubMed1981

Enrichment of human basophils.

A 3-step procedure is described in detail for producing 50% basophils in 50% yield from human blood. Leukocytes from dextran sedimented blood or preferably whole blood are sedimented on Hypaque-Ficoll, then on aqueous Hypaque, followed by adherence and elution from a column of glass beads. The cells appear normal and undergo specific histamine release after incubation with antigen. The procedure is relatively rapid and should allow further study of mechanisms of mediator release with more homogeneous populations of basophils. The first step also provides a 5 min separation of blood into a lymphocyte enriched mononuclear cell fraction and a granulocyte enriched fraction.

Basophils↗
PubMed1981

An agent that releases basophil and mast cell histamine but blocks cyclooxygenase and lipoxygenase metabolism of arachidonic acid inhibits immunoglobulin E-mediated asthma in rhesus monkeys.

An inhibitor of the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism, BW755C, was evaluated with the rhesus monkey model of IgE-mediated asthma. BW755C was found to release histamine from human and rhesus peripheral blood leukocytes and rhesus bronchial lavage cells. BW755C did not induce a rhesus airway response but inhibited antigen-induced airway changes in pulmonary resistance and dynamic compliance. The results demonstrated that a lipoxygenase and cyclooxygenase inhibitor that is a histamine releaser may inhibit some pulmonary function abnormalities of an IgE-mediated response and suggested that histamine has a minor role as a stimulator of airway reaction in this model. This was supported by studies showing failure of the histamine H1 blocker pyrilamine maleate to inhibit the antigen-induced airway response. Although BW755C has been shown to be a lipoxygenase and cyclooxygenase inhibitor, it is not established that the inhibiting action of this agent on an antigen-induced airway response is due to an effect on arachidonate metabolism in the lung.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1981

Seasonal variation of IgE antibody specific for ragweed antigen E (IgE-a-AgE) from the basophil surface in patients with ragweed pollenosis.

Seasonal elevation in total serum IgE and IgE antibody specific for antigen E (IgE-a-AgE) are well recognized in patients with ragweed pollenosis. We found that the ratio of specific IgE-a-AgE to total IgE in plasma was the only measure predictive of the number of specific IgE-a-AgE molecules per basophil. Although both total and specific IgE rose with season, the ratio did not change, the number of IgE-a-AgE molecules per basophil did not change, and histamine release in response to AgE did not increase.

Antibody Specificity↗
PubMed1980

Immunoglobulin E-mediated asthma and hypersensitivity pneumonitis with precipitating anti-hapten antibodies due to diphenylmethane diisocyanate (MDI) exposure.

Two workers are presented who were exposed to diphenylmethane diisocyanate (MDI) while coating pipes with a polyurethane foam. After a latent period of exposure, worker A developed immediate-onset asthma and worker B developed a clinical picture of hypersensitivity pneumonitis for which he was hospitalized. The antibody response of these workers to a conjugate of MDI with human serum albumin (MDI-HSA) was measured by gel precipitation, total antibody binding of 125I MDI-HSA, and specific IgG and IgE antibody by polystyrene-tube radioimmunoassay (PTRAI). Worker B had precipitating antibody to MDI-HSA by double immunodiffusion in gel. Both workers had high levels of IgG antibody specific for MDI-HSA which had some cross-reactivity with a conjugate or toluene diisocyanate and HSA. Total serum antibody binding of 125I MDI-HSA was 15 microgram/ml in worker A and 900 microgram/ml in worker B. Both workers had serum IgE antibody specific for MDI-HSA as measured by two PTRIA techniques. These results indicate that a marked immunologic response to MDI is possible in exposed workers and that hypersensitivity pneumonitis can occur subsequent to the inhalation of a low-molecular-weight chemical in the industrail setting.

Adult↗