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Basophil sensitization for food allergens in idiopathic nephrotic syndrome.

To estimate food sensitization, the human basophil degranulation test (HBDT), usually used for allergy diagnosis, was performed in 34 idiopathic nephrotic syndrome (INS) patients, classified as minimal change glomerular disease, with or without atopic manifestations, and in 19 blood donors; five food allergens (wheat flour, cow's milk, whole egg, beef and pork) were investigated. The HBDT was positive in 22 out of the 34 INS (64%) and in 1 out of the 19 blood donors (p less than 0.001). The test was 9 times positive for wheat flour, 9 times for pork, 6 times for cow's milk, 6 times for beef and 5 times for whole egg. Moreover in 13 cases, the basophil sensitization was present for two or three of these food allergens in the same patient. A direct causal relationship between food sensitization and INS cannot be drawn from this study: it might be demonstrated only by elemental or oligoantigenic diet prior to specific avoidances.

Allergens↗

A patient with basophilic-eosinophilic myeloproliferative disorder showing monosomy 7 and hyperhistaminemia.

We encountered a male patient with marked basophilia and eosinophilia complicated by anemia, thrombocytopenia, myelofibrosis, and hyperhistaminemia. Since morphological abnormalities were unclear and since chromosome analysis showed 45,XY,-7, a diagnosis of basophilic-eosinophilic myeloproliferative disorder was made. After administration of prednisolone and cytarabine ocfosfate, basophil and eosinophil levels decreased, but blasts transiently appeared in the peripheral blood. Chromosome analysis performed at the time of appearance of blasts showed a clone with 45,XY,-7,del(16)(q22). Subsequently, pancytopenia developed, after which white blood cell count and its classification were normal, as were chromosome findings. In this patient, monosomy 7 seemed to have induced myeloproliferative disorder with basophilia and eosinophilia, and del(16)(q22) may have enhanced the eosinophilia.

Aged↗

Evidence for the neoplastic involvement of monocytic, eosinophilic and basophilic lineages in acute myelomonocytic leukemia with eosinophilia.

To investigate the origin of cells observed in acute myelomonocytic leukemia with eosinophilia (M4E0), we carried out morphological and cytogenetic studies of colonies derived from leukemic precursors. Marrow cells from a patient with M4E0 at second relapse revealed an abnormal karyotype; 47,XY, +8, inv(16)(p13q22), 17p-. Cytogenetic studies of leukemic colonies showed the same karyotypic abnormality. The primary and secondary colonies consisted of monocytes, eosinophils and basophils. These results indicated that the neoplastic process in this patient originated in a stem cell capable of differentiation into at least monocytes, eosinophils and basophils.

Adult↗

Unique serum requirement for histamine release from human basophils.

Basophil histamine release in a patient with an IgE-mediated seminal plasma allergy had a requirement for serum. Washed leukocytes, in the absence of serum, released little histamine on challenge with seminal plasma antigen. The addition of serum markedly enhanced the release. However, serum had only a mild effect on ragweed antigen induced histamine release from the same cells of this individual. Serum from normal donors was equally effective as autologous serum. Heating the serum and treating it with mercaptoethanol did not destroy this activity. The serum effect was unique in that another patient with seminal plasma allergy did not demonstrate this phenomenon. It is postulated that the effect of the serum is to stabilize the antibody-antigen step at the basophil surface.

Basophils↗

Passive sensitization of human basophils: evidence for heterogeneity in the IgE molecule.

Possible functional heterogeneity of human IgE antibody was studied by passively sensitizing human basophils for antigen-induced histamine release. Six sera of known IgE anti-ragweed antigen E and total IgE content were diluted to contain 10 ng of antibody but differed with respect to the ratio of specific/total IgE. The relative ability of the sera to passively sensitize generally reflected the specific/total IgE ratio but one serum was 2.5 times more active than the remainder. This ability did not reflect the IgG antibody level nor was it due to a dialyzable or heat-stable factor. These data indicate functional IgE heterogeneity, probably due to the interaction of the Fc portion of IgE with the basophil receptor.

Basophils↗

IgE-mediated histamine release from human basophils: differences between antigen E- and anti-IgE-induced secretion.

The mechanism of the IgE-mediated release of histamine from human basophils differs when the process is initiated by antigen as compared to anti-IgE (a-IgE). Antigen causes release from the basophils of different individuals over a wide range of concentrations, while release to a-IgE occurs over a limited concentration range; antigen excess inhibition is also relatively slight as compared to that observed with a-IgE. Release by antigen occurs with a shorter lag period and a more rapid rate than seen with a-IgE. Agonists which inhibit release by acting through adenylate cyclase (dimaprit, adenosine, isoproterenol) are significantly more potent with respect to antigen than to a-IgE-induced release. Other agonists (3-isobutyl-1-methylxanthine, dibutyryl cyclic AMP) which increase cyclic AMP by different mechanisms are equally effective against antigen and a-IgE, suggesting that the receptor-adenylate cyclase interactions differ between the two stimuli. The cyclooxygenase inhibitor, indomethacin, consistently enhances antigen- but not a-IgE-induced release while cytochalasin B, which acts in part on microfilaments, enhances both processes equally. These data indicate that cross-linking of surface antibody IgE by antigen initiates a release process different from that caused by a-IgE, perhaps because the former is a multivalent ligand and the latter is functionally bivalent.

1-Methyl-3-isobutylxanthine↗

IgG4 and passive sensitization of basophil leukocytes.

In contrast to IgE, myeloma IgG4 did not block passive sensitization of basophil leukocytes by IgE antibody. Atopic sera, selected for a high level of mite-specific IgG4, lost their sensitizing activity after they had been heated at 56 degrees C. After incubation of leukocytes with myeloma IgG4 or with sera with high levels of specific IgG4, the cells did not become responsive towards anti-IgG4 antiserum. After incubation of leukocytes with fluorescein-labelled myeloma IgE, these cells released histamine with antifluorescein antiserum. In contrast, after incubation with fluorescein-labelled myeloma IgG4, a subsequent incubation with antifluorescein antiserum did not result in histamine release. Therefore, we cannot confirm the hypothesis of Vijay and Perelmutter that IgG4 can sensitize basophil leukocytes in vitro.

Basophils↗

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↗

Subthreshold and suboptimal desensitization of human basophils. II. Nonspecificity and irreversibility of desensitization.

Desensitization in human basophils was induced by suboptimal levels of antihuman IgE or antigen under normal calcium buffer conditions. Low doses of anti-IgE triggered only 0-12% histamine release during a 3-hour preincubation, yet initiated up to 100% desensitization upon rechallenge. After 24-27 h preincubation with allergen a, the cells did not regain releasability when rechallenged with either allergen a, allergen b or anti-IgE. Low dose, IgE-mediated desensitization in human basophils may lead to an irreversible and nonspecific inhibition of degranulation.

Basophils↗

On the secretory process of rat mast cells and rat basophilic leukaemia cells. Effects of aggregated IgGa on 45Ca influx and histamine secretion.

The biological role of heat-aggregated IgGa during the secretory process of rat mast cells and rat basophilic leukaemia (RBL) cells was analysed. Incubation of normal rat mast cells and rat basophilic leukaemia cells with heat-aggregated IgGa alone leads to a stabilization of the cells resulting in a reduction of mediator secretion and ion influx. When mast cells from Nippostrongylus brasiliensis-infected animals were incubated with heat-aggregated IgGa and subsequently challenged with anti-IgE, a dual effect with regard to ion influx and histamine release was observed, depending on the concentration of heat-aggregated IgGa or anti-IgE either a pronounced decrease or a marked enhancement was apparent. Our data suggest that heat-aggregated IgGa as well as immune complexes modulate the secretory response of mast cells and may thus play an important role in the allergic disease process.

Animals↗

Inhibition of IgE-mediated histamine release from human basophils and mast cells by fenoterol.

Fenoterol, a beta 2-adrenergic agonist recently introduced to treat asthmatic disorders, inhibits antigen-induced histamine release from human basophil leukocytes and lung mast cells in a dose-dependent fashion. The dose-response inhibition curve is paralleled by a fenoterol-induced increase in the cAMP levels of human leukocyte preparations. The relationship between the effect of fenoterol and cAMP level is supported by the finding that the beta 2-adrenergic agonist only inhibits the first stage of antigen-induced histamine release and not the release caused by the Ca2+ ionophore, A23187. Propranolol, a competitive antagonist of beta 2-adrenergic receptor, blocks the inhibition of release and the cAMP accumulation caused by fenoterol. Finally, theophylline, a cAMP phosphodiesterase inhibitor, synergistically potentiates the inhibitory effect of fenoterol on histamine release and the accumulation of cAMP. These data suggest that fenoterol may modulate the in vivo release of the mediators of immediate hypersensitivity reactions via the activation of beta 2-adrenergic receptor linked to adenylate cyclase on human basophils and mast cells.

Adolescent↗

Studies on human basophil releasability.

Basophil releasability is an important parameter in several pathophysiological conditions. In normal donors, the maximum percent histamine release and cell sensitivity to rabbit anti-Fc epsilon (anti-IgE) is correlated with the age of cell donors. A positive correlation between serum IgE level and anti-IgE-induced histamine release was found in subjects below 20 years old. The response to formyl-Met-Leu-Phe (f-met peptide) was significantly reduced in subjects above 60 years old. In twins, IgE-mediated releasability and serum IgE levels appear to be controlled by two different genetic mechanisms. Basophils of patients with atopic dermatitis were more responsive than those of control subjects of matched ages to anti-IgE.

Adolescent↗

Activation of human basophils by bacterial products.

Staphylococcus aureus Cowan I (Cowan Staph A+), which synthesizes protein A (Staph A), induced histamine release from human basophils. In contrast, S. aureus Wood 46 (Wood Staph A-), which does not synthetize Staph A, did not induce histamine secretion. Soluble Staph A and Cowan Staph A+ induced histamine release by interacting with the alternative F(ab')2-binding site of IgE and/or IgG present on human basophils. Pepstatin A, a pentapeptide synthetized by various actinomycetes, induced histamine secretion by activating a specific membrane receptor, which is also activated by synthetic formylmethionine-containing peptides.

Basophils↗

Inhibition of human basophil leukotriene release by antiinflammatory steroids.

We have previously shown that 24-hour culture of human basophils with the antiinflammatory steroid dexamethasone produces an inhibition of the IgE-dependent release of histamine. In contrast, similar treatment of purified human lung mast cells does not inhibit the subsequent release of either histamine, prostaglandin D2, or leukotriene (LT) C4. We now show that incubation of mixed leukocytes for 24 h with 10(-7) M dexamethasone produces an inhibition of anti-IgE-induced basophil LTC4 release as detected by radioimmunoassay. In three experiments, control (CON) and dexamethasone (10(-7) M; DEX)-treated cells were challenged with 0.01, 0.03 and 0.1 micrograms/ml of anti-IgE, and histamine and LTC4 were monitored. LTC4 release (ng LTC4/micrograms total cell histamine) from cells stimulated with anti-IgE was: 0.01 micrograms/ml anti-IgE, 6.9 +/- 4, 0.3 +/- 0.1 (CON, DEX); 0.03 micrograms/ml anti-IgE, 13.8 +/- 4.7, 0.9 +/- 0.5; 0.1 micrograms/ml anti-IgE, 19.5 +/- 2.3, 4.9 +/- 1.2. Histamine release was inhibited by 50-75% by treatment with DEX in these experiments. Dose-response studies (n = 4) indicate that the inhibitory actions of DEX on LTC4 release occur in the range of 10(-10) to 10(-7) M. The concentration of DEX at which LTC4 release was inhibited by 50% (IC50) was approximately 2 X 10(-9) M. Another glucocorticoid (betamethasone) inhibited LTC4 release, while the nonglucocorticoids tetrahydrocortisone and beta-estradiol were inactive. High performance liquid chromatography (HPLC) analysis (coupled with RIA) indicated that the relative proportions of LTC4, LTD4, and LTE4 did not differ in supernatants from CON- and DEX-treated, anti-IgE-challenged cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents↗

Partial separation and functional characterization of guinea pig basophil-stimulating factor.

We have previously described T lymphocyte dependent guinea pig basophil growth from bone marrow precursors in vitro. In the current studies, basophil-stimulating factor (BSF) present in mitogen-stimulated splenic conditioned medium (CM) has been functionally characterized, utilizing an assay for BSF on nonadherent bone marrow target cells. BSF was found to be heat stable, nondialyzable, and inactivated by proteases. Monosaccharides known to inhibit guinea pig lymphokines yielded a unique profile of inhibition of BSF activity and nonidentity of BSF with guinea pig migration inhibition factor, interleukins 1 or 2, and granulocyte-macrophage colony-stimulating activity, from which BSF could be separated after gel filtration. BSF-containing CM also had no detectable interleukin-3 activity as measured in a murine assay. An inverse relation was found between interleukin 2 and BSF production by peritoneal exudate T cells (PEL) stimulated with antigen. Fractionation of serum-containing and serum-free CM demonstrated a molecular size for BSF of 50,000-65,000 daltons. Guinea pig BSF is a distinct T cell dependent lymphokine with an active protein moiety which may interact with target bone marrow cells through a cell surface carbohydrate receptor.

Animals↗

Effect of glycoprotein-processing inhibitors on the mouse IgE binding capacity of rat basophilic leukemia cells.

The basophile surface high affinity receptors for IgE (Fc epsilon R) are heavily glycosylated glycoproteins like the IgE Fc itself. Their functional expression in their physiological environment can be studied with the help of a recently developed CELISA (ELISA on cell) methodology. The relevance of the IgE and Fc epsilon R glycans for their interaction in situ has been probed using inhibitors of discrete trimming steps of N-linked carbohydrate processing. The IgE produced by mouse hybridoma cells in the presence of deoxynojirimycin (dNM), a glucosidase I inhibitor, keeps intact both its antigen and Fc epsilon R-binding capacities. Rat basophilic leukemia (RBL) cells cultured in presence of dNM or of another glucosidase I inhibitor, castanospermine (Cs), show marked decreases in their capacity to bind mouse monoclonal IgE. In contrast, their culture in the presence of either deoxymannojirimycin (dMM) or swainsonine (Sw) either does not affect or even slightly increases the membranous expression of Fc epsilon R capable to bind mouse IgE.

1-Deoxynojirimycin↗

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↗

Seasonal patterns of circulating basophils.

The seasonal patterns of circulating basophils were investigated in a sample of 33,000 French subjects, aged 20-60 years. Circannual variations (minimum in October, maximum in July) which might be related to pollens were observed. Periods with cold weather (temperature below 0 degrees C) correlated to a temporary rise in basophils.

Adult↗