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Biomedical subjects

B S Bochner

Publications and source records attributed to B S Bochner.

107 records · Page 6Linked to original sources
PubMed1991

Altered surface expression of CD11 and Leu 8 during human basophil degranulation.

Immunofluorescence and flow cytometric techniques have been used to study changes in surface Ag expression and viability that occur during human basophil degranulation. Treatment with polyclonal anti-IgE, FMLP, or the calcium ionophore A23187 induced histamine release, along with rapid and sustained unimodal increases in basophil CD11b mean fluorescence intensity. In contrast, treatment with anti-IgE or FMLP resulted in a decrease in Leu 8 expression. Degranulation did not significantly affect basophil viability (as determined by exclusion of propidium iodide), scatter characteristics, or percentage of identifiable IgE-bearing cells, and an inconsistent association was seen between percent histamine release and reduction in the percent of cells identified by light microscopy after staining with alcian blue. For anti-IgE, dose-dependent changes in CD11b, CD11c, and Leu 8 expression were seen (optimal at 0.1, 0.1, and 1 microgram/ml, respectively), although CD11a expression remained unchanged. Histamine release was optimal at 0.3 microgram/ml anti-IgE, and at superoptimal concentrations, reduced CD11b expression was observed which paralleled decreases in histamine release; reduction of the expression of Leu 8, however, occurred equally at optimal and superoptimal concentrations of anti-IgE. Kinetic analyses of these responses revealed that CD11b up-regulation proceeded more rapidly than histamine release, whereas Leu 8 down-regulation was much slower and did not plateau until 120 min of stimulation. Although changes in CD11b mean fluorescence intensity correlated with the magnitude of histamine release, exposure to stimuli in the absence of calcium (which blocked degranulation) resulted in similar alterations in CD11b and Leu 8, suggesting that degranulation was not required for changes in the surface expression of these adhesion molecules. Interestingly, pretreatment of basophils with drugs that either inhibited or enhanced histamine release (isobutylmethylxanthine and cyclosporin A vs cytochalasin B, respectively) significantly decreased the magnitude of anti-IgE-induced CD11b up-regulation; down-regulation of Leu 8 expression was also partially inhibited by treatment with isobutylmethylaxanthine. These studies demonstrate that activation of human basophils by secretagogues in vitro results in a variety of phenotypic changes including alterations in surface expression of adhesion molecules, and suggest that degranulation in vivo may be accompanied or preceded by changes in adhesion-related functions.

Antigens, Differentiation↗
PubMed1991

Episodic eosinophilia-myalgia-like syndrome in a patient without L-tryptophan use: association with eosinophil activation and increased serum levels of granulocyte-macrophage colony-stimulating factor.

We have studied a patient with recurrent bouts of angioedema, myalgia, and eosinophilia that was not due to L-tryptophan ingestion. Peripheral blood eosinophils (EOSs) during exacerbations of his illness displayed characteristics of "activation," including hypodense phenotype and increased responsiveness to platelet-activating factor (PAF) in vitro with respect to expression of CD11b surface adhesion proteins. Elevated serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) bioactivity were also detected, whereas interleukin-3 and interleukin-5 levels were not increased. During treatment with glucocorticoids, all clinical symptoms resolved, EOSs decreased in number and became normodense, PAF responsiveness diminished, and GM-CSF levels returned to normal. During glucocorticoid tapering, a subsequent clinical relapse was again associated with EOS hypodensity, increased PAF responsiveness, and increased serum GM-CSF levels. Although this patient satisfies the diagnostic criteria for eosinophilia-myalgia syndrome, the episodic and profound nature of exacerbations and response to therapy in the absence of L-tryptophan usage suggests a possible overlap with the syndrome of episodic angioedema and eosinophilia. In vitro studies suggest that GM-CSF may play a role in the eosinophilia, EOS activation, and pathophysiology of disease in this patient and demonstrate resolution of these abnormalities during glucocorticoid therapy. The efficacy of glucocorticoid therapy in some hypereosinophilic states may therefore be mediated, at least in part, via reduction of GM-CSF production and/or EOS activation.

Angioedema↗
PubMed1991

The role of basophils in asthma.

The characteristics of the acute and late human response to antigen in the upper and lower airways and in the skin is summarized in TABLE 2. This table makes it clear that while mast cells are responsible for the mediator release of the acute phase, eosinophils and basophils are the cells involved in the mediator release which occurs during the experimental late phase reaction. The pattern of mediators observed during the acute response is quite characteristic of the mast cell. Thus, in the nose, skin, and lungs, the acute response is characterized by significant increases in histamine, PGD2, tryptase, and sometimes LTC4. In the late phase reaction, the pattern of mediator release is characteristic of basophils and eosinophils, and includes histamine, LTC4 (where measurable), and eosinophil-derived proteins, without PGD2 or tryptase. Basophils have been identified at appropriate time-points in each model using morphologic and phenotypic criteria, and their numbers relate to the histamine levels. Finally, treatment with glucocorticosteroids, the most potent drugs available for treating chronic allergic inflammation, obliterates the late phase reaction and decreases both mediator release and the infiltration of eosinophils and basophils. Chronic allergic inflammation is now taken by both the pulmonary and immunologic community as a hallmark of asthma, and it can be stated without equivocation that the basophils are responsible for the mediator release observed in that response.

Asthma↗
PubMed1990

IL-3 augments adhesiveness for endothelium and CD11b expression in human basophils but not neutrophils.

A number of natural and recombinant human cytokines have been tested for their ability to activate basophil and neutrophil adhesiveness for human umbilical vein endothelial cells in vitro. Coincubation of basophils and endothelial cell monolayers for 10 min with biologically relevant concentrations of rIL-1, natural IL-2, rIL-4, rIL-5, rIL-6, rIL-8, rGM-CSF, and rIFN-gamma had no effect on basophil adhesiveness. In contrast, rIL-3 induced basophil adhesiveness for endothelial cells (optimal at 1 ng/ml: 144 +/- 18% of control adherence (mean +/- SEM); control basophil binding, 13 +/- 3%, n = 9, p less than or equal to 0.05). This increase in adhesiveness was similar in magnitude to that induced by an optimal concentration of a known potent inducer of basophil adhesiveness (1 microM FMLP, 164 +/- 15% of control adherence, n = 9). Under these experimental conditions, the effects of rIL-3 occurred at concentrations of 0.1 to 30 ng/ml, were partially dependent on calcium, and were not accompanied by histamine release. Fixation experiments demonstrated that the effect of rIL-3 was directed against the basophil rather than the endothelial cell. Neither rIL-3 nor the other cytokines tested had any effect on the adherence of 51Cr-labeled neutrophils, even when tested simultaneously on cells from the same donors. Under experimental conditions that permitted histamine release, no correlation was seen between the ability of rIL-3 (0.3 to 300 ng/ml) to induce histamine release or enhance adhesiveness (n = 8). mAb blocking experiments demonstrated a role for both CD11 and CD18 adherence glycoproteins in basophil adherence induced by rIL-3, and indirect immunofluorescence and flow cytometric analysis revealed that rIL-3 treatment led to rapid and sustained increases in cell surface expression of CD11b antigens on basophils but not neutrophils (e.g., after 10 min: 217 +/- 29 vs 91 +/- 11% of control mean fluorescence intensity, p less than 0.05). However, no correlation was seen between the magnitude of changes in CD11b expression and changes in adhesion when tested simultaneously. These results suggest that local production of IL-3 during allergic reactions in vivo may selectively promote basophil activation, adhesion to endothelium, and recruitment to extravascular sites of inflammation.

Antigens, Differentiation↗
PubMed1990

Interleukin-1 is released at sites of human cutaneous allergic reactions.

Interleukin-1 (IL-1) promotes cell recruitment and influences allergic mediator release. We analyzed histamine, prostaglandin D2, IL-1, and leukocytes accumulating hourly for 12 hours at skin-chamber sites after local ragweed challenge in eight allergic subjects with cutaneous late-phase reactions. Ragweed induced a peak of histamine at 1 hour (p less than 0.02), which diminished, and then steadily increased (p less than 0.02). Prostaglandin D2 levels peaked by the second hour (p less than 0.02) and then decreased, approaching prechallenge levels by 12 hours. Leukocyte infiltration (predominantly neutrophils) was detectable 3 to 4 hours after challenge, although selective enrichment of mononuclear cells, eosinophils, and basophils ws observed at later hours (p less than 0.02). IL-1 bioactivity was detected in fluids 10 to 12 hours after challenge but not at control sites (p less than 0.05). Analysis of IL-1 beta levels by RIA revealed an initial peak at 1 hour of 0.90 ng/ml (p less than 0.02) and a second elevation of up to 0.75 ng/ml during the later hours (p less than 0.04). Ragweed challenge of three nonatopic subjects did not change levels of the above-mentioned mediators or cells. Bioactivity in chamber fluids from antigen-challenged sites of atopic subjects was significantly neutralized by an anti-IL-1 beta antiserum, although treatment with anti-IL-1 alpha and anti-IL-1 beta was needed for complete neutralization, IL-1 released locally during cutaneous allergic reactions may contribute to IgE-dependent cutaneous inflammation.

Adolescent↗
PubMed1989

Flow cytometric methods for the analysis of human basophil surface antigens and viability.

Fluorescence and flow microfluorometric methods have been established for the detection and evaluation of IgE-bearing human leukocytes in various cell preparations including those where basophils are present at low percentages. Quantitative techniques for the determination of basophil purity, viability, and cell surface antigens including IgE are described. Use of these methods will facilitate the identification and phenotypic analysis of human IgE-bearing cells in a wide variety of biological fluids.

Antigens, CD↗
PubMed1989

IgE-dependent regulation of human basophil adherence to vascular endothelium.

Mechanisms favoring the recruitment of circulating human basophils to extravascular sites of allergic inflammation are unknown. The basophil secretagogues anti-IgE, and pollen allergens rye grass I and ragweed Ag E (Lol p I and Amb a I) were tested for their ability to promote basophil adherence to umbilical vein endothelial cells. Co-incubation of endothelial cells and basophils with anti-IgE resulted in time and dose-dependent increases in basophil adhesion. These effects were due to activation of the basophil, required both magnesium and calcium, occurred before or in the absence of histamine release, and were seen at concentrations of stimulus below the usual range of secretagogue activity. In contrast, anti-IgE or Ag stimulation of neutrophils, or basophils from donors non-responsive to anti-IgE or Ag with respect to histamine release, had no effect on cell adherence. mAb 60.3, recognizing the CD18 leukocyte adhesion molecule, inhibited anti-IgE-induced enhancement of basophil-endothelial cell binding. Exposure of basophils to low concentrations of Ag in vivo may selectively initiate basophil infiltration into tissue sites of allergic inflammation by enhancing their adherence to endothelium.

Adjuvants, Immunologic↗
PubMed1988

Adherence of human basophils to cultured umbilical vein endothelial cells.

The mechanism by which circulating human basophils adhere to vascular endothelium and migrate to sites of allergic reactions is unknown. Agents have been identified which stimulate the adherence of purified basophils to cultured human umbilical vein vascular endothelial cells (HuVEC). Treatment of HuVEC with interleukin 1, tumor necrosis factor (TNF), bacterial endotoxin, and 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in time and dose-dependent increases of adhesiveness for basophils. Coincubation of basophils and HuVEC for 10 min with C5a, formyl-methionyl-leucyl-phenylalanine, the calcium ionophore A23187, platelet-activating factor, TNF, and TPA also resulted in significant dose-dependent increases in basophil adherence; this effect resulted from activation of the basophil. Adherence of basophils to HuVEC was time and temperature dependent, required divalent cations, and was unaffected by glucocorticoids. Monoclonal antibody 60.3, directed against the beta-subunit of the leukocyte adherence complex CD18, inhibited the binding of basophils to HuVEC. Adherence of basophils to vascular endothelium may be important in initiating basophil infiltrates in vivo.

Basophils↗
PubMed1987

Interleukin 1 production by human lung tissue. I. Identification and characterization.

Crucial to the development of inflammatory infiltrates is the localized production of mediators which promote adherence of leukocytes to the vascular endothelium. Previous in vitro studies, using monolayers of cultured human vascular endothelial cells (VEC), have identified various agents which promote the acquisition of adhesiveness in VEC for polymorphonuclear leukocytes. In the present studies, we report that human lung fragments cultured for 4 to 24 hr release a factor which acts on VEC to promote adherence of polymorphonuclear leukocytes. Adhesiveness in VEC stimulated by lung fragment culture supernatants was time- and dose-dependent. This adherence-promoting factor appears to be a mixture of the alpha and beta forms of interleukin 1 (IL-1) and has the following properties: 1) it is heat-labile; 2) it is not inactivated by polymyxin B; 3) it has mobility on Sephadex G-75 column chromatography corresponding to apparent m.w. of approximately 15,000, 30,000, and 70,000 (a pattern observed previously for IL-1); 4) it has activity in the thymocyte costimulation IL-1 assay, but no interleukin 2 activity, and 5) it is neutralized by anti-human IL-1 antisera but not by anti-human tumor necrosis factor antiserum. Production and release of IL-1 in vivo may play a role in the development of inflammatory infiltrates in human lung and other tissues by acting on endothelium to promote the localized adherence of leukocytes.

Cell Adhesion↗
PubMed1987

Interleukin 1 production by human lung tissue. II. Inhibition by anti-inflammatory steroids.

Glucocorticoids block the localized accumulation of leukocytes as sites of inflammation by preventing their adherence to vascular endothelium. This implies that glucocorticoids are acting either on the leukocytes, endothelium, or cells which produce adherence-promoting factors (such as interleukin 1 (IL-1)). Previous studies have shown that dexamethasone (DEX) treatment of either polymorphonuclear leukocytes (PMN) or human umbilical vein vascular endothelial cells (VEC) or both in vitro does not prevent adherence induced by thrombin or formylmethionyl-leucyl-phenylalanine (f-met peptide). We now show that pretreatment of PMN and/or VEC for 24 hr with 0.1 microM DEX had no effect on adherence of PMN to VEC activated with IL-1 (2 U/ml), lipopolysaccharide (1 microgram/ml), or 12-O-tetradecanoylphorbol-13-acetate (30 ng/ml) suggesting that glucocorticoids may inhibit adherence in vivo by blocking formation of IL-1 and other adherence-inducing stimuli. We have recently established that cultured human lung fragments produce IL-1 in vitro. To investigate whether glucocorticoids could inhibit the production of adherence-inducing factors, we examined the effect of glucocorticoids on IL-1 production from human lung tissue. Treatment of human lung fragments in vitro for 18 hr with glucocorticoids such as DEX and hydrocortisone resulted in dose dependent inhibition of IL-1 production; these and other glucocorticoids, at concentrations ranging between 0.1 and 1 microM, produced greater than 50% inhibition of IL-1 release. Nonglucocorticoid steroids including testosterone and beta-estradiol (1 microM) had no effect. Inhibition of IL-1 production occurred after a lag period 5 of 16 hr, and the relative glucocorticoid potencies agreed with their known anti-inflammatory potencies in vivo (beta-methasone approximately triamcinolone acetonide greater than DEX greater than fludrocortisone greater than prednisolone greater than hydrocortisone). Inhibition of IL-1 production in vivo may, in part, explain the remarkable ability of glucocorticoids to prevent the adherence of leukocytes to endothelium and their accumulation at an inflammatory site.

Anti-Inflammatory Agents↗
PubMed1984

Effect of the calcium ionophore A23187 and aspirin on histamine release in vitro from leukocytes of aspirin-intolerant donors.

In vitro histamine release from leukocytes of 10 aspirin-intolerant donors in response to the calcium ionophore A23187 and aspirin was compared to that of controls. Incubation with A23187 induced a concentration-dependent histamine release from leukocytes of all donors. At 0.1 and 0.2 micrograms/ml A23187, release from leukocytes of aspirin-intolerant donors was significantly less (p less than 0.01) than that of controls. Preincubation with aspirin failed to alter spontaneous or A23187-stimulated histamine release. Leukocytes of aspirin-intolerant donors do not demonstrate an enhanced sensitivity to histamine release stimulated by aspirin or A23187.

Adult↗