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L M Lichtenstein

Publications and source records attributed to L M Lichtenstein.

At least 55 records · Page 3Linked to original sources
PubMed1997

Differential efficacy of lymphocyte- and monocyte-selective pretreatment with a type 4 phosphodiesterase inhibitor on antigen-driven proliferation and cytokine gene expression.

Elevations of intracellular cyclic AMP, achieved with the use of phosphodiesterase (PDE) inhibitors, cause functional downregulation of most inflammatory cells. Rolipram, an inhibitor selective for the PDE4 isozyme, can markedly downregulate antigen-driven proliferation and cytokine gene expression of unfractionated human peripheral blood mononuclear cells. However, it is unclear whether PDE4 inhibitors in a mixed-cell system exert their immunosuppressive effect on the lymphocyte or on the monocyte fraction. We have used an adherence-based protocol for separating peripheral blood mononuclear cells, isolated from atopic individuals, into lymphocyte and monocyte fractions and have selectively treated these populations with rolipram prior to reconstituting the cell cultures to their original lymphocyte/monocyte proportions. Cellular responses to both ragweed and tetanus toxoid were analyzed for both proliferation and gene expression of proinflammatory cytokines. A dose-dependent downregulation of ragweed- and tetanus toxoid-driven proliferative responses was achieved by pretreatment of lymphocytes from peripheral blood with rolipram. This downregulation was significantly greater than that achieved with pretreatment of monocytes. Pretreatment of both populations failed to show synergistic downregulation of proliferation. Lymphocyte pretreatment with rolipram also resulted in marked downregulation of gene expression for IL-4, IL-5, and interferon-gamma compared to monocyte pretreatment in both ragweed- and tetanus toxoid-driven systems. Interestingly, monocyte pretreatment in these systems resulted in significant downregulation of IL-2 gene expression compared to lymphocyte pretreatment. Flow cytometric analysis failed to show alterations in any of a panel of surface activation and signal transducing molecules by rolipram treatment with or without antigen stimulation. We conclude that, in a mixed cell system, PDE4 inhibitors downregulate antigen-driven proliferation and gene expression of proinflammatory cytokines predominantly through their effects on lymphocytes rather than monocytes.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Treatment with hot, humid air reduces the nasal response to allergen challenge.

Ten subjects with asymptomatic seasonal allergy, outside of their allergy season, underwent allergen provocation following 1 hour of exposure to air at either 20 degrees C and 30% relative humidity (RH) or air at 37 degrees C and 90% RH. The ipsilateral changes following antigen challenge were compared under the two conditions. Conditioning of the nose to 37 degrees C, 90% RH reduced total histamine release (7.9 +/- 1.8 ng vs 4.2 +/- 1.3 ng; p < or = 0.05), sneezes (6 +/- 2 vs 3 +/- 1; p < or = 0.05), pruritus (score of 17.4 +/- 6.0 vs score of 2.0 +/- 1.8 out of a total score of 100, p < or = 0.01), nasal airway resistance (1.4 +/- 0.8 kPa/L/sec vs 0.2 +/- 0.1 kPa/L/sec; p < or = 0.05), human serum albumin levels (389.6 +/- 53.4 micrograms vs 242.2 +/- 37.9 micrograms; p < or = 0.05), and congestion (score of 23.8 +/- 4.8 vs score of 10.6 +/- 5.4 out of a total score of 100, p < or = 0.01). It had no effect on the volume of secretions (p = 0.8), lactoferrin levels (p = 0.3), or rhinorrhea (p = 1.0). Thus air at 37 degrees C and 90% RH partially reduces the early response to antigen. Its effects are greatest on histamine release, the vascular response, and neural responses, with no effect on the glandular response. The mechanisms underlying these effects are unknown.

Adult↗
PubMed1997

Anaphylaxis during autologous peripheral blood progenitor cell infusion.

Anaphylaxis has been reported in subjects receiving peripheral blood precursor cell (PBPC) infusions; however the etiologic agent is unclear. Basophils from a PBPC-allergic subject were challenged with each individual component of the stem cell infusion and with recombinant human (rh)DNAse. Histamine release data were compared with those using basophils from control subjects. Histamine release assays were repeated using basophils from a control subject passively sensitized with serum IgE from the patient. Skin testing with bovine DNAse was performed using standard techniques. Basophil histamine release occurred in the patient, but not in controls, with bovine DNAse. No release could be provoked by any of the other components of the infusate; no release could be detected with rhDNAse. Sensitivity to bovine DNAse could be transferred to basophils from a control subject with the serum IgE from the patient. Marked epicutaneous skin test reactivity to bovine DNAse was evident in the patient, but not in control subjects. We conclude that systemic reactions during peripheral blood precursor cell infusions may represent true IgE-mediated anaphylaxis to bovine DNAse in the infusate. Skin testing can detect such sensitivity, and the use of rhDNAse may obviate such reactions.

Anaphylaxis↗
PubMed1997

Vesicular transport of Charcot-Leyden crystal protein in f-Met peptide-stimulated human basophils.

The ultrastructural localization of Charcot-Leyden crystal (CLC) protein during f-Met-peptide-induced degranulation of human basophils was analyzed at multiple times after stimulation. In this secretion model, piecemeal and anaphylactic degranulation occurred sequentially in stimulated cells and were followed by reconstitution of granule contents. This analysis showed that granule number and alteration and location of gold-labeled, formed CLCs changed over time. CLCs were extruded from granules and remained attached to plasma membranes early after stimulation. At later times, similar structures reappeared in granules in quantity. Smooth-membrane-bound vesicles, analyzed by number, by visible particle contents (or lack of contents) and by gold labeling for CLC protein, showed that empty vesicles increased at the earliest time sampled (0 time) and plunged thereafter in actively extruding and completely degranulated cells. Vesicles containing granule particles were elevated initially at 10 s and at later times. Gold-labeled CLC-protein-containing vesicles were of either empty or particle-filled varieties, and both types were involved with CLC protein transport out of cells at early times and into cells at later times as basophils recovered. Thus, vesicle transport of CLC protein is a mechanism for producing piecemeal degranulation and endocytotic recovery of released CLC protein from human basophils. This vesicular shuttle may be an effector mechanism for widespread piecemeal losses from granules in basophils in inflammatory sites in vivo in human disease.

Anaphylaxis↗
PubMed1997

Bilateral increases in histamine after unilateral nasal allergen challenge.

Studying the inflammatory response that follows the early response to nasal challenge with antigen provides a better understanding of allergic rhinitis than just studying the immediate (early) response. Nine allergic volunteers were challenged unilaterally with antigen-containing discs, and bilateral changes in physiologic responses as well as in the concentration of histamine in nasal secretions were measured for 11 h. We found significant immediate increases in symptoms, sneezes, ipsilateral nasal airway resistance, and ipsilateral histamine in the early phase response. Two-thirds of the allergen-challenged volunteers showed increases in physiologic parameters or histamine in the hours after allergen challenge. The pooled data of all subjects exhibited significant increases in bilateral nasal airway resistance and in ipsilateral and contralateral histamine, hours after unilateral provocation. These responses differed significantly from control subjects. In another group of 11 volunteers challenged ipsilaterally with antigen, the number of basophils increased both on the side of challenge and on the contralateral side. The magnitude of the increase on the ipsilateral side correlated with the increase on the contralateral side (r(s) = 0.72). The basophils are the most likely source of the contralateral increase in histamine as they are on the ipsilateral side. Although the mechanisms underlying this contralateral increase in basophils and histamine are not known, we speculate that delayed, neurogenic responses play a contributory role.

Adult↗
PubMed1997

Differential regulation of human, antigen-specific Th1 and Th2 responses by the B-7 homologues, CD80 and CD86.

A selectivity of B7.1 (CD80) for promoting Th1 responses and B7.2 (CD86) for promoting Th2 responses in the murine system has recently been suggested. The present study explores this hypothesis, using human PBMCs and antigen-specific Th1 and Th2 clones. Proliferative responses of peripheral blood mononuclear cells (PBMCs) from ragweed-allergic, tetanus toxoid-immunized individuals were downregulated by treatment with anti-CD86 in ragweed- and tetanus toxoid-driven cultures (% Inhibition = 55 +/- 4 and 61 +/- 12, respectively; P < 0.03 relative to untreated cultures). Gene expression in PBMCs for interleukin (IL)-4, IL-5, and interferon gamma (IFNgamma), assessed by reverse-transcriptase polymerase chain reaction, was also downregulated by treatment with anti-CD86 in both the ragweed- and tetanus toxoid-driven systems. Neither independent efficacy nor synergy with anti-CD86 was apparent with anti-CD80 treatment; two different anti-CD80 blocking antibodies yielded identical results. Conversely, antigen-specific Th1 and Th2 clones were insensitive to treatment with either anti-CD80, anti-CD86, or a combination of the two. Unaffected parameters included proliferative response (P < 0.14 and 0.33, respectively, for Th1 and Th2), proinflammatory cytokine gene expression, and cytokine protein secretion into culture supernatants (P < 0.44 and 0.16, respectively, for IL-4 and IFNgamma). We conclude that CD86 is the primary B7 signaling homologue in human PBMC responses, and that second signal pathways through the B7 homologues have no effect on phenotypically differentiated T helper cells in humans.

Antigens, CD↗
PubMed1997

Localization of Charcot-Leyden crystal protein in individual morphological phenotypes of human basophils stimulated by f-Met peptide.

BACKGROUND: Human basophils undergo anaphylactic degranulation, characterized by extrusion of membrane-free granules, and piecemeal degranulation, characterized by progressive removal of granule contents in the absence of granule extrusion. F-Met peptide stimulates a degranulation continuum in human basophils that includes both forms of secretion. Charcot-Leyden crystal protein is stored in the granules of unstimulated human basophils. OBJECTIVE: The objective of this study was to determine the subcellular localization of the Charcot-Leyden crystal protein in individual morphological basophil phenotypes that are stimulated by f-Met peptide and are associated with secretion. METHODS: A post-embedding immunogold analysis was used to detect changes in the subcellular sites of Charcot-Leyden crystal protein in human basophils stimulated with f-Met peptide. Human basophils from normal donors were purified by countercurrent centrifugal elutriation and Percoll density gradients, stimulated to degranulate with 1 micron f-Met peptide (or incubated in buffer controls), and recovered for histamine assay, electron microscopy and immunogold labelling. Specificity controls included omission of the primary antibody and substitution of the primary antibody with non-immune normal rabbit IgG or with Charcot-Leyden crystal protein-Sepharose-absorbed primary antibody. RESULTS: The results showed new sites of labelling and different densities of labelling for Charcot-Leyden crystal protein in distinctive basophil phenotypes stimulated by f-Met peptide. New sites for Charcot-Leyden crystal protein included nucleus, cytoplasm, degranulation channel, degranulation channel membrane, plasma membrane, and a newly recognized granule population similar to primary granules in eosinophils. These new sites, as well as previously documented sites of Charcot-Leyden crystal protein (granules, intragranular Charcot-Leyden crystals, cytoplasmic vesicles) showed variable labelling when analysed by phenotype. Other sites (besides intragranular Charcot-Leyden crystals) of formed Charcot-Leyden crystals included cytoplasm, degranulation channel, extracellular space and, rarely, nucleus. Analysis of cytoplasmic vesicles, total granules and altered granules, and gold particles in subcellular compartments in seven identifiable phenotypes revealed that f-Met peptide stimulated human basophils to empty their granules by transporting Charcot-Leyden crystal protein in vesicles to the plasma membrane in the absence of granule extrusion in cells exhibiting piecemeal degranulation. In cells exhibiting anaphylactic degranulation, gold-labelled Charcot-Leyden crystals were extruded to the cells' exterior in concert with granule particles and concentric dense membranes contained within granules. Completely degranulated cells had a high density of plasma membrane gold label that was associated with numerous gold-laden endocytotic cytoplasmic vesicles. Basophils reconstituted their main granule population, within which Charcot-Leyden crystals resided, in part by endocytosis of previously released plasma membrane-bound Charcot-Leyden crystal protein. Completely recovered cells displayed decreased Charcot-Leyden crystal protein labelling of the plasma membrane and vesicle compartments, the presence of a highly labelled new granule subset that resembled Charcot-Leyden crystal protein-containing primary granules in eosinophils, and the highest density of granule and intragranular Charcot-Leyden crystal gold labelling of all phenotypes that developed after stimulation. CONCLUSION: Seven individual f-Met peptide-activated human basophil phenotypes labelled by an ultrastructural immunogold method to detect subcellular sites of Charcot-Leyden crystal protein showed changing distributions of this protein which document the capability of human basophils to undergo complex release and recovery reactions that may be pertinent to the functions of Charcot-Leyden crystal protein and the capabilit

Anaphylaxis↗
PubMed1997

Differential regulation of human antigen-specific Th1 and Th2 lymphocyte responses by isozyme selective cyclic nucleotide phosphodiesterase inhibitors.

Our study explores the relative efficacy of phosphodiesterase (PDE) inhibitors on antigen-specific Th1 and Th2 clonal responses. Proliferative responses for both phenotypes were down-regulated by the PDE4 inhibitor, rolipram, but not the PDE3 inhibitor, siguazodan. The Th2 clones were more sensitive than the Th1 clones to PDE4 inhibition (P < .05 at 10 and 100 microM rolipram). The addition of 1 microM of the adenylyl cyclase activator, isoproterenol, significantly decreased both the EC50 and IC50 of rolipram in both phenotypes (P < .05). Gene expression for interleukin-4, interleukin-5, or interferon-gamma, assessed by reverse transcription-polymerase chain reaction, was down-regulated by the PDE4 inhibitor, but not the PDE3 inhibitor, in each respective clone. Cytokine protein secretion paralleled the results of reverse transcription-polymerase chain reaction for IL-4 and interferon-gamma (P < .01 for each). No differential efficacy on cytokine generation parameters between T helper phenotypes was apparent. Rolipram treatment significantly elevated intracellular cyclic AMP (adenosine 3',5'-cyclic monophosphate) in clonal T cells (P < .01 for Th1 or Th2 clones); these elevations were consistently greater in the Th2 clones (P < .05). Finally, Th1 cells showed reduced gene expression for the PDE4C isoform and a lack of gene expression for the PDE4D isoform by reverse transcription-polymerase chain reaction, compared to the Th2 cells. These data demonstrate the potent immunomodulatory efficacy of PDE4 inhibition on antigen-specific T cell clones. The enhanced sensitivity of Th2 cells to PDE4 inhibition may be due, in part, to the differential expression of PDE4 isoforms between Th1 and Th2 cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Vesicular transport of histamine in stimulated human basophils.

Human basophils participating in experimentally produced contact allergy display progressive secretion of electron-dense secretory granule contents and retention of cytoplasmic granule containers in the absence of entire granule extrusion, a process termed piecemeal degranulation (PMD) and postulated to be effected by vesicular transport (Dvorak HF, Dvorak AM: Clin Hematol 4:651, 1975). Proof of this hypothesis was sought using models of human basophil-stimulated secretion, partially purified human peripheral blood basophils, and a morphometric analysis of the fraction of total cellular cytoplasmic vesicles loaded with histamine, a major proinflammatory mediator present in basophil secretory granules. The subcellular localization of histamine was accomplished using a new ultrastructural enzyme-affinity-gold method based on the affinity of diamine oxidase for its substrate, histamine (Dvorak et al: J Histochem Cytochem 41:787, 1993). Two models were selected for a kinetic analysis of stimulated vesicle transport of histamine based on known biochemical and ultrastructural characteristics (MacGlashan et al: J Immunol 136:2231, 1986; Warner et al: J Leukoc Biol 45:558, 1989; Dvorak et al: Am J Pathol 141:1309, 1992; Dvorak et al: Lab Invest 64:234, 1991). These models were selected to include the rapid release reaction stimulated by the bacterial peptide, FMLP, and the slow release reaction stimulated by the phorbol diester tumor promoter, TPA. The results of this study showed that the fraction of histamine-loaded cytoplasmic vesicles (%VG/TV/micron2) in TPA-stimulated basophils significantly exceeded the fraction in unstimulated cells, a process that persisted for 45 minutes after TPA stimulation and was associated with extensive PMD and no morphologic evidence of recovery. Similarly, the fraction of histamine-loaded cytoplasmic vesicles after FMLP stimulation significantly exceeded the fraction in unstimulated cells, a process that persisted for 10 minutes after FMLP stimulation and was associated with the morphologic continuum of PMD-->anaphylactic degranulation (characterized by extrusion of granules)-->recovery, a process largely complete in the 10-minute samples. These studies establish for the first time that an important proinflammatory mediator, histamine, traffic from secretory granules to the extracellular milieu in small cytoplasmic vesicles in stimulated human basophils. The association of this process with the ultrastructural release reaction defined as PMD produced primarily by TPA and in part by FMLP establishes vesicular transport as the mechanism for effecting this type of regulated secretion. Vesicular transport of histamine was also significant in the more complex stimulated secretory and recovery model produced by exposure of human basophils to the bacterial peptide FMLP.

Basophils↗
PubMed1996

An immunoglobulin E-dependent recombinant histamine-releasing factor induces interleukin-4 secretion from human basophils.

A novel recombinant histamine-releasing factor (rHFR), which stimulates secretion from a subpopulation of human basophils that express a particular type of immunoglobulin E (IgE) or IgE+, was found to induce interleukin-4 (IL-4) production from cells isolated from these same donors. The secretion of IL-4 protein induced by rHRF significantly correlated with histamine release and the amount of protein generated, and the kinetics were identical to those caused by anti-IgE activation. Furthermore, the ability of rHRF to induce IL-4 protein production from cells not normally responsive to this protein was transferred by passive sensitization with plasma containing IgE+ antibody. That this novel protein stimulates both mediator release and the secretion of IL-4 protein from human basophils suggests a prominent role for this molecule in allergic disease.

Basophils↗
PubMed1996

Effects of loratadine and terfenadine on the induced nasal allergic reaction.

OBJECTIVE: To evaluate the effect of terfenadine and loratadine on the early nasal allergic response to challenge and the subsequent cellular influx and hyperresponsiveness. DESIGN: Double-blind, placebo-controlled, triple-crossover study. SUBJECTS: Fourteen, asymptomatic, allergic volunteers. INTERVENTIONS: After an initial challenge with methacholine chloride, subjects received treatment with placebo, loratadine (10 mg by mouth daily), or terfenadine (60 mg by mouth twice daily) for 1 week, followed by a nasal allergen challenge with lavages; 24 hours later, while the subjects were still receiving medication, the quantity of cells in the nasal lavage was determined, and another challenge with methacholine was done. Mediator levels were quantified in the nasal lavages after the allergen c hallenge, and the weight of the methacholine-induced nasal secretions was measured. RESULTS: Both loratadine and terfenadine treatment resulted in significant reductions in allergen-induced sneezing and the levels of histamine, kinins, albumin, and N-alpha-tosyl-L-arginine methyl ester-esterase activity in recovered nasal lavages compared with the reductions that resulted from placebo treatment, with no significant difference among the treatments. Treatment had no effect on the levels of tryptase, prostaglandin D2 or leukotriene C4. A significant eosinophil influx into nasal secretions 24 hours after the allergen challenge in patients who were receiving placebo (P=.006) was not affected by loratidine or terfenadine treatment. Comparing methacholine-induced secretions between screening challenges and challenges with the patients who were being treated with either loratadine or terfenadine, there was a significant decrease in secretions after the use of these antihistamines (P<.05). CONCLUSION: Both loratadine and terfenadine partially inhibit the early nasal response to allergen challenge and the subsequent reactivity to a challenge with methacholine without affecting the influx of eosinophils into nasal secretions.

Adult↗
PubMed1996

Diamine oxidase-gold ultrastructural localization of histamine in isolated human lung mast cells stimulated to undergo anaphylactic degranulation and recovery in vitro.

A new enzyme-affinity-gold ultrastructural method makes use of the affinity of the enzyme, diamine oxidase coupled to gold, for its substrate, histamine, for localization of histamine in isolated human lung mast cells (HLMCs). The method works with routinely prepared ultrastructural samples, thereby allowing precise identification of ultrastructural structures that contain histamine. We used this method to identify the release of histamine from granule stores in anti-immunoglobulin-E (IgE)-stimulated HLMCs and the replacement of histamine in secretory granules of HLMCs during recovery from anaphylactic degranulation in vitro. The findings show that electron-dense granules in unstimulated HLMCs, maintained up to 24 h in culture, and in responding anti-IgE-stimulated HLMCs, over the same time period in vitro, contained histamine. Alteration of granules, resulting in decreased electron density of their contents, was associated with decreased label for histamine. Electron-lucent intracytoplasmic degranulation chambers were devoid of histamine. Recovering HLMCs developed new granule stores of histamine by a mixture of conservation, synthetic, and endocytotic mechanisms.

Amine Oxidase (Copper-Containing)↗
PubMed1996

Substance P activates the release of histamine from human skin mast cells through a pertussis toxin-sensitive and protein kinase C-dependent mechanism.

Using pharmacologic agents, we explored the mechanism by which a potent neuropeptide, substance P, induces the secretion of histamine from human skin mast cells and compared their effects on substance P-induced histamine release to the secretion activated by anti-IgE. Histamine release from human cutaneous mast cells induced by substance P was inhibited by the Ge-protein inhibitor pertussis toxin that, in turn, did not affect the IgE-mediated secretion. Similarly to anti-IgE, two activators of protein kinase C, tetradecanoylphorbol acetate (TPA) and bryostatin 1, significantly inhibited the substance P-induced response. In contrast, drugs that enhance intracellular levels of cAMP, an inhibitor of protein kinases, genistein, and a protease inhibitor, AEBSF, did not affect substance P-induced histamine secretion, whereas these compounds significantly reduced the response initiated by anti-IgE. Our data demonstrate that substance P activates human cutaneous mast cells by acting on G proteins and protein kinase C. Our results also suggest that the biochemical pathways underlying mast cell activation by substance P and anti-IgE are to a great extent unrelated.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Comparative ultrastructural morphology of human basophils stimulated to release histamine by anti-IgE, recombinant IgE-dependent histamine-releasing factor, or monocyte chemotactic protein-1.

An ultrastructural analysis of human basophils stimulated with anti-IgE, recombinant histamine-releasing factor (rHRF), or monocyte chemotactic protein-1 (MCP-1) (compared with unstimulated cells) was performed. Partially purified peripheral blood basophils were prepared for electron microscopy at time points known to precede histamine release and at half-maximum histamine release times for each secretagogue. Activation morphologies associated with stimulation included granule-vesicle attachments, piecemeal degranulation, anaphylactic degranulation, and uropod formation. These features were qualitatively similar in the stimulated samples. Quantitative differences were evident, however, when stimulated samples were compared with controls or at different time points after stimulation with a single agent or when individual secretagogues were compared. All stimulated samples differed quantitatively from the control samples. Rank orders for morphologic activation events revealed that the most effective trigger for anaphylactic degranulation was anti-IgE > MCP-1 > rHRF, whereas the most effective trigger for uropod formation was rHRF > anti-IgE > MCP-1. Rank orders for piecemeal degranulation and granule-vesicle attachments were the same: MCP-1 > anti-IgE > rHRF. Important relationships among these anatomic events reveal that the development of motile configurations is not associated with the development of secretion morphologies and that piecemeal degranulation precedes and is inversely related to anaphylactic degranulation in stimulated samples.

Antibodies, Anti-Idiotypic↗
PubMed1996

Lectins do not distinguish between heterogenous IgE molecules as defined by differential activity of an IgE-dependent histamine releasing factor.

It has been suggested that differential histamine-releasing activity of an IgE-dependent histamine-releasing factor (HRF), which has recently been cloned, is related to carbohydrate difference in the IgE molecule. Lectins are able to recognize specific glycoforms and might therefore be useful in characterizing the proposed heterogeneity of IgE molecules. As one test of this hypothesis, we examined the histamine release potency of several well-characterized lectins on basophils passively sensitized with serum containing IgE molecules that support HRF-induced histamine release (IgE+) or serum that does not support release by this stimulus (IgE-). Histamine release was induced by challenging basophils with different concentrations of concanavalin A, Lens culinaris (LcH), and Pisum sativum (PSA). Dose-response curves revealed that LcH caused 30% histamine release at 2 micrograms/ml with IgE+ sensitized cells, whereas the same release with IgE- cells required sixfold higher concentrations. Similar values for PSA showed a sevenfold difference. With concanavalin A, the selectivity was reversed in that it was fourfold more active on IgE- -sensitized cells. Another pair of sera (IgE+ vs IgE-) revealed the same result for concanavalin A, but no difference occurred in LcH and PSA induced release between the IgE+ - and IgE- -sensitized cells. These contrasting findings with different pairs of IgE+ -and IgE- -containing sera indicated that the lectins LcH and PSA are not able to discriminate between IgE+ -and IgE- -sensitized cells as does HRF and therefore cannot be used to further define the proposed heterogeneity of IgE. this conclusion was supported by experiments in which basophil preparations from donors possessing natural sensitivity or insensitivity to HRF (having IgE+ or IgE- on their surface) were examined fro their response to these lectins. No difference was found in the sensitivity of the cells to challenge with LcH or PSA, and the response to concanavalin A was the opposite of that found when passively sensitized cells were used (30% histamine release at 0.9 vs 3.5 micrograms/ml for IgE+ vs IgE- donors, respectively). We conclude that oligosaccharide-specific lectins do not differentiate between HRF-reactive and HRF-nonreactive IgE molecules on basophils.

Basophils↗
PubMed1996

Successful parenteral desensitization to paclitaxel.

BACKGROUND: Paclitaxel, a member of a new class of antineoplastic agents called the taxanes, has been associated with anaphylactoid reactions. OBJECTIVE: We report a case of successful parental desensitization to paclitaxel. METHODS: Desensitization was performed with serial 10-fold dilutions (up to 1:100,000) of paclitaxel in sufficient volume to administer successive doses of 1, 2, 4, and 8 ml. Basophil histamine release tests were performed with paclitaxel alone, vehicle alone, and paclitaxel and vehicle combined to determine which agent was responsible for the anaphylactoid reactions. RESULTS: After parental desensitization was performed, the patient was able to tolerate infusion of paclitaxel without complications or need for antihistamines or steroids. Basophil histamine release occurred only with paclitaxel and not with the vehicle. CONCLUSIONS: Successful parenteral desensitization to paclitaxel can be achieved; it is paclitaxel, and not its vehicle, that is most likely responsible for anaphylactoid reactions in patients undergoing treatment.

Adult↗