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Basophil leucocytes in responses to parasitic infection and some other stimuli in sheep.

Basophil leucocytes are a significant component of the infiltrating cells in a variety of tissue reactions in guinea pigs. However, little is known about the participation of basophils in similar reactions in most other animal species. The circulating blood, skin and small intestinal mucosa of sheep were examined after they had received stimuli known to elicit basophil-rich responses in guinea pigs but relatively few basophils were found.

Animals↗

Enhanced basophil releasability in subjects infected with human immunodeficiency virus.

Spontaneous histamine release and basophil response to IgE-dependent (anti-IgE) and IgE-independent (formyl-methionine peptide, calcium ionophore A23187) stimuli were evaluated in 15 patients with acquired immunodeficiency syndrome (AIDS), 8 with AIDS related complex (ARC), 7 with lymphadenopathy syndrome (LAS), 11 seropositive asymptomatic subjects, 10 human immunodeficiency virus (HIV)-seronegative drug addicts, and 20 normal subjects. Both spontaneous histamine release and anti-IgE-induced histamine release were significantly increased in HIV-infected subjects, in comparison with seronegative drug addicts and normal controls. Basophil response to anti-IgE was higher in AIDS/ARC patients than in seropositive asymptomatic subjects and LAS patients, although the difference was not statistically significant. When basophils were challenged with 0.1 microM formyl-methionine peptide, a significantly increased histamine secretion was found in HIV-infected subjects; conversely, at the higher formyl-methionine peptide concentration (10 microM), as well as at all calcium ionophore A23187 concentrations, histamine release was similar in all the studied groups. No correlation was found among anti-IgE-induced histamine release, total lymphocyte counts, CD4+ and CD8+ T cell counts, and total serum IgE levels. These findings indicate that infection with HIV is associated with an increased basophil releasability. This could be of some relevance in the increased incidence of allergic manifestations and adverse drug reactions observed in AIDS patients.

AIDS-Related Complex↗

The direct basophil degranulation test and the intracutaneous test: a comparison using food extracts.

The purpose of this study was to compare the direct basophil degranulation test (DBDT) of Hirsch and Zastrow with the intracutaneous (IC) test in subjects with and without histories of food allergy. The DBDT was perfomred by incubating the concentrated leukocytes of subjects with dilutions of the suspected allergenic extract and comparing the number of nondegranulated basophils remaining in the test samples with the number remaining in a control. The test sample with the least number of basophils represents maximal basophil degranulation. The DBDT was perfromed with extracts of the suspected food on 14 subjects with reliable clinical histories and positive IC tests indicative of food hypersensitivity. Thirteen of these 14 food-sensitive subjects also had IC and DDBT8 to the extracts of foods to which they were not clinically sensitive. Fourteen different subjects not allergic to foods were also tested with food extracts by the IC and DBDTS. There was a 92% correlation between the IC test and the DBDT, a 90% correlation between the IC test and the history, and an 86% correlation between the DBDT and the history. We conclude that, in this study of subjects clearly sensitive to foods, the DBDT correlates favorably with the history and IC test.

Allergens↗

Exercise and isocapnic hyperventilation-induced bronchoconstriction in asthma: relevance of circulating basophils to measurements of plasma histamine.

The relationship of airway cooling during exercise to changes in airway caliber, plasma histamine levels, and circulating basophils was investigated in eight allergic asthmatic and eight normal subjects. In asthma matched RHE during exercise and ICH produced almost identical bronchoconstriction with maximum falls in SGaw of 61.0 +/- 4.5% and 57.9 +/- 5.2%, respectively. A similar RHE in normal subjects was associated with a 7.9 +/- 3.3% fall in SGaw. The resting plasma-histamine levels were higher in the asthmatic (0.52 +/- 0.06 ng/ml) than in the normal (0.31 +/- 0.07 ng/ml, p less than 0.05) subjects. No significant change in plasma histamine occurred after exercise in either group nor in the asthmatic subjects with ICH. In contrast, exercise but not ICH stimulated an increase in leukocytes, basophils, and total blood histamine in parallel with the airway response that reached a maximum at 2 to 5 min in both normal and asthmatic subjects. There was a positive correlation between basal plasma and total blood-histamine levels (r = 0.67, p less than 0.01) in normal and asthmatic subjects suggesting that basophils contribute significantly to plasma histamine. The spontaneous basophil release of histamine was greater in asthmatic (13.4 +/- 2%) than in normal subjects (6.46 +/- 7%, p less than 0.005), which is consistent with the higher resting plasma-histamine levels in the asthmatic subjects. These findings suggest that plasma-histamine changes with exercise in asthma but not ICH may be related to the associated basophilia and sample handling rather than intrapulmonary mast cell degranulation.

Adult↗

Increased numbers of circulating basophil progenitors in atopic patients.

Recruitment of basophils to sites of homocytotropic antibody-mediated hypersensitivity reactions has been well documented in both experimental and clinical situations. Mechanisms underlying tissue basophil accumulation, however, remain unclear and may involve chemotaxis, cell proliferation, or both. We have recently reported the presence in human blood of circulating basophil/mast cell progenitors on the basis of histamine content of granulocyte colonies grown in methylcellulose. In the current studies we have analyzed the peripheral blood of 30 patients with atopy and 25 comparable control subjects for frequency of basophil/mast cell progenitors by analysis of the histamine content of individual granulocyte colonies. Forty percent of granulocyte colonies in cultures of atopic patients contained histamine in comparison to only 11% in cultures of control subjects (p less than 0.001). Histamine content per colony as well as mean histamine per cell in each colony was higher in granulocyte colonies of atopic subjects and could not be related to colony size or culture conditions. Granulocyte colony growth was enhanced by antigen-stimulated, peripheral blood lymphomononuclear cell--conditioned media of atopic patients. Histamine-positive colonies were found more frequently in active versus quiescent atopic disease (p less than 0.05). These results are consistent with the hypothesis that basophils accumulate at sites of allergic reactions at least in part by recruitment of progenitors from circulation and subsequent differentiation in situ in response to lymphokines. Further studies by use of hemopoietic assays could elucidate the contribution of basophil production to the development of allergic conditions.

Adolescent↗

Basophil histamine release remains unaffected by clinical desensitization to penicillin.

A penicillin-allergic patient who required therapy with beta-lactam antibiotics was desensitized with increasing parenteral doses of benzylpenicillin. After desensitization, the patient tolerated, without signs of allergic reaction, intravenous piperacillin. Immunologic studies were undertaken to investigate humoral and cellular changes accompanying desensitization. Serum penicilloyl IgG and IgE antibodies did not change significantly during induction of clinical tolerance to the drug. The patient's previously positive immediate skin reaction to penicilloyl polylysine (PPL) converted to negative. Nonspecific releasability of skin mast cells as tested with polymyxin B skin test was unchanged. In contrast, in vitro blood basophil activation, both by specific antigen (penicilloyl-human albumin) and a nonspecific IgE-dependent stimulus (anti-IgE) remained strong after the desensitization procedure and during weeks of high-dose piperacillin therapy. A monovalent penicilloyl hapten inhibited penicilloyl-albumin-induced basophil histamine release, whereas the patient's own serum taken while the patient was receiving treatment did not. Moreover, the patient's treatment serum, while the patient was receiving piperacillin, was able to trigger histamine release from passively sensitized basophils of a donor not allergic to penicillin, suggesting the presence of a sufficient amount of complete multivalent antigen to initiate release and/or desensitization. The presence of high concentrations of penicilloated serum proteins in the patient's treatment serum was confirmed by immunoassay. Basophil histamine release could, nevertheless, be elicited from the patient's whole blood sample taken while the patient was receiving piperacillin treatment by adding penicilloyl-human albumin in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Interaction of paramyxoviruses with human basophils and their effect on histamine release.

We have demonstrated that human peripheral blood basophils released histamine on direct incubation with paramyxoviruses in vitro. Most histamine release occurred during the first 15 to 30 minutes after challenge, depending on the dose of virus used; release initiated by virus was complete by 1 hour. At a virus/cell ratio of 1:1, Sendai virus caused 41 +/- 9% histamine release, whereas parainfluenza type 3 (PI-3) virus caused 25 +/- 5% release and respiratory syncytial (RS) virus caused 19 +/- 5% release. Sendai, but not PI-3 or RS, also caused a decrease in cell number and release of lactic dehydrogenase; however, this apparent cell lysis did not account for all the histamine released. Incubation of cells with virus desensitized them to subsequent triggering by viruses but did not affect response of cells to other stimuli. Histamine release was dependent on the virus/cell ratio, temperature, and metabolic energy, but it was not strictly dependent on the presence of calcium in the extracellular medium. Histamine release was not affected by preincubation of cells with colchicine, suggesting that microtubules were not involved in the release process. Basophils desensitized by anti-IgE in the absence of calcium or treated with lactic acid to dissociate IgE molecules from membrane receptors released amounts of histamine similar to that of control basophils; thus, release was not initiated through Fc epsilon receptors. It was found, however, that histamine release by these viruses was greatly reduced when concanavalin A was used for desensitization. These data demonstrate that the respiratory viruses studied can cause direct nonimmunologic release of histamine from human basophils. Our findings provide evidence for another mechanism by which respiratory viruses can initiate inflammation.

Adult↗

In-vitro culture of basophils from human bone marrow.

An in-vitro culture system is described in which metachromatically granulated leucocytes differentiate from human bone marrow under stimulation by conditioned medium from the 5637 cell line. By morphological, cytochemical and immunophenotypic criteria these were shown to be basophils, rather than mast cells. This system may prove useful in studies of basophil differentiation, and in characterisation of growth factors active upon basophil precursors. The study also identified the 5637 bladder carcinoma cell line as a constitutive producer of basophil growth factor(s); this may represent a convenient source for the isolation and purification of such factors.

Basophils↗

Anti-immunoglobulin induced histamine release from naturally abundant basophils in the snapping turtle, Chelydra serpentina.

The dose response, temperature sensitivity, time course and calcium dependency of histamine release from snapping turtle basophils treated with rabbit anti-turtle immunoglobulin (RATIg) sera was explored. This investigation indicated that the level of histamine release induced by RATIg was dependent upon the concentration of RATIg with concentrations of 350 mcg/ml inducing optimal release. In addition, release was temperature dependent with release increasing over a temperature range of 10 degrees C to maximal at 27 degrees C. Release was also dependent on the length of exposure to RATIg. Release increased steadily over a time period of 0 to 30 minutes with the higher concentrations of RATIg inducing the most rapid release. Basophil-histamine release was also found to be calcium dependent. This study indicates that the snapping turtle basophil possesses similar characteristics to that of its mammalian counterparts. It is proposed that the very wide temperature range over which turtle basophils release histamine is an important feature in he immune resistance of this ectothermic animal.

Animals↗

The role of basophils in the immunopathogenesis of hypersensitivity to fleas (Ctenocephalides felis) in dogs.

Biopsies taken of skin test sites from 10 dogs allergic to fleas were fixed in Karnovsky's fixative and embedded in methacrylate. One micron sections were stained with acid Giemsa for identification of basophils. This cell was identified in most biopsies taken at intervals from 1 hour to 48 hours post-injection. The proportion was highest between 4 hours and 18 hours and had substantially fallen by 48 hours. The highest number of basophils recorded as a percentage of the inflammatory infiltrate was 22.1%, with biopsies from 7 of the 10 dogs showing in excess of 10% basophils at some point. The results suggest that cutaneous basophil hypersensitivity may play an immunopathogenic role in flea-bite hypersensitivity in dogs.

Animals↗

The relationship between interleukin-3-like activity and basophil production in chronic myeloid leukemia patients.

Increased basophil proliferation has been reported in patients with chronic myeloid leukemia (CML) both in vivo and in vitro. In this study we have examined the relationship between the release of interleukin-3-like activity (IL-3-LA) by mononuclear cells derived from CML patients and the development of basophils under culture conditions. The results indicate that cells from CML patients produce a high percentage of basophils under the applied experimental conditions. The IL-3-LA in the conditioned medium (CM) of these patients was much lower than that of the controls. Incubation of cells from CML patients with CM containing IL-3-LA resulted in its absorption, whereas cells from control subjects did not absorb the factor. This result may explain the discrepancy between the high basophil production and the low IL-3-LA observed in the CML patients and may indicate that leukemic cells possess receptors for IL-3-LA.

Basophils↗

Voltage-dependent ion channels on human basophils: do they exist?

The presence of voltage-dependent ion channels (particularly Ca2+ channels) on the surface of 'non excitable' cells such as human basophils is a matter of debate. Indeed, in basophils, Ca2+ entry or mobilization is not sufficient by itself to trigger secretion, although enhanced cytosolic Ca2+ concentration increases it. In order to address this question, we used a two-signal model and we report here experiments which suggest the presence of voltage-dependent structures directly or indirectly linked to membrane Ca2+ pathways. Indeed, it is known that, in the presence of PMA at threshold concentration (1st signal), elevation of cytosolic Ca2+ (2nd signal) induces histamine release. We observed that a depolarizing external solution (high K+) induced a Ca(2+)-dependent release of histamine from PMA-treated human basophils. High K+ alone did not induce histamine release. Although the voltage-sensitive component and the physiological relevance of this mechanism remain to be defined, these results suggest that this voltage-dependent Ca2+ influx in the human basophil could contribute to the up-regulation of histamine release.

Basophils↗

Effect of nedocromil sodium and cromoline sodium on atopic basophil function.

Nedocromil sodium (NS) is a new drug for the treatment of bronchial asthma. In the present study, we examined the effect of NS on basophil histamine release stimulated by anti-IgE, anti-IgE+IL-3 (interleukin-3) or ryegrass. The effect of cromoline Na (CrS) on histamine release from basophils to the same stimuli was compared. NS did not affect histamine release from basophils following anti-IgE alone or together with IL-3, but augmented the release following ryegrass. CrS did not affect histamine release after the same three stimuli. We concluded that NS and CrS do not affect bronchial asthma through direct inhibition of histamine release from basophils. Their action may be via an indirect effect on histamine-releasing factor.

Adolescent↗

Ionic regulation of human basophil releasability. III. Effects of Na+ and Ca2+ on histamine release induced by different stimuli.

The effects of Na+ and Ca2+ ions on histamine release from human basophils stimulated by anti-IgE, N-formyl-methionyl-leucyl-phenylalanine (FMLP), 4 beta-phorbol 12-myristate 13-acetate (PMA) and Ca2+ ionophore A23187 were evaluated. Isosmotic replacement of Na+ in the extracellular medium with the nonpermeant Na+ analogue choline+ or with glucose led to a significant increase in anti-IgE- (1/5000: 43.7 +/- 7.3% in high Na+ vs 68.9 +/- 7.3% in low Na+, mean +/- SEM, n = 8, P < 0.001), FMLP- (1 microM: 37.9 +/- 2.3% vs 49.5 +/- 4.3%, n = 8, P < 0.01) and PMA-(160 nM: 12.7 +/- 0.9% vs 27.3 +/- 4.3%, n = 8, P < 0.05) induced histamine release, whereas A23187-induced histamine release was reduced (1 microM: 90.4 +/- 2.4% vs 45.4 +/- 3.4%, n = 8, P < 0.0001). The progressive increase in extracellular Na+ concentration was accompanied by a decrease of basophil response to anti-IgE, FMLP and PMA; in contrast, A23187-induced histamine release was up-regulated by Na+. The Na+/H+ exchanger monensin, in the concentration range of 10(-8)-10(-4) M, exerted a dose-dependent inhibitory effect on anti-IgE-, FMLP- and PMA-induced histamine release, but not on A23187-induced histamine release. Extracellular Ca2+ up-regulated the histamine release induced by all the above stimuli. Removal of extracellular Na+ lowered the requirement of extracellular Ca2+ for anti-IgE, FMLP- and PMA-induced histamine release. In contrast with previous observations showing that Na+ supports histamine release from rat peritoneal mast cells and rat basophilic leukaemia cells, these results indicate that Na+ strongly inhibits histamine release from human basophils stimulated by anti-IgE, FMLP and PMA, whereas it enhances Ca2+ ionophore A23187-induced histamine release. The effects of Na+, which are probably related to modulation of membrane potential and/or intracellular pH, vary depending on the cell type and the stimulus employed for cell activation.

Antibodies↗

Luteolin, a flavonoid, inhibits AP-1 activation by basophils.

Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.

Basophils↗

Monosomy 7 as the sole abnormality of an acute basophilic leukemia.

We report the case of a 72-year-old man who had the very rare disease acute basophilic leukemia with the sole chromosomal finding of a monosomy 7. Most nuclear cells in the peripheral blood and bone marrow samples were either basophils or blasts. The blasts showed negative reaction with myeloperoxidase, periodic acid Schiff, chloroacetate esterase, alpha-naphthyl butyrate esterase, acid phosphatase, and Sudan black B. Metachromatic features of the blasts, however, were observed with toluidine blue stain. Electron microscopic evaluation showed the typical ultrastructure, with basophil and immature mast cell granules. Cytogenetic study revealed monosomy 7 in all metaphase cells, and this finding was confirmed by fluorescence in situ hybridization. The Philadelphia chromosome was absent. Review of the literature revealed abnormalities in cases of ABL. To our knowledge, the case reported here is the first to have basophilic leukemia with monosomy 7 as the only chromosome abnormality.

Aged↗

Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on basophils.

BACKGROUND: Omalizumab is a monoclonal anti-IgE antibody that is effective for the treatment of allergic respiratory disorders; however, its onset of action is unknown. OBJECTIVE: This study was designed to determine the onset of action of omalizumab through the use of a challenge model to determine time-dependent inhibition of ragweed-induced changes in nasal volume as well as correlate the kinetics of omalizumab-induced decreases in serum free IgE and FcepsilonRI receptors on basophils. METHODS: We conducted a 6-week, randomized, double-blind, placebo-controlled study of 24 rhinitic patients with ragweed allergy. After PD(30) ragweed nasal allergen challenge, patients received either omalizumab, approximately 0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were rechallenged with ragweed PD(30) dose biweekly. FcepsilonRI expression on blood basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days after treatment. IgE levels were measured at baseline and on days 3, 28, and 42. RESULTS: Mean IgE levels decreased by 96% (P <.001) from baseline within 3 days in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was decreased to 20.4% at 7 to 14 days (P <.001) and 12.2% at 35 to 42 days (P <.001) for the omalizumab group. There was a median decrease in basophil FcepsilonRI expression of 73% (P <.001) in the omalizumab group, with maximum inhibition occurring within 14 days of treatment. No significant changes in IgE levels, nasal allergen challenge responses, or basophil FcepsilonRI expression were observed throughout the study in the placebo group. CONCLUSIONS: Our study showed that the onset of action by omalizumab in blunting ragweed-induced nasal responses is within 2 weeks, and this response was associated with 2 putative mechanisms of action: decreased serum free IgE and decreased FcepsilonRI receptor expression on immune effector cells.

Adult↗

Assays for measuring in vitro basophil activation induced by recombinant allergens.

The diagnosis of type I allergy is essentially based on clinical data, skin tests, and measurements of allergen-specific IgE. However, the determination of specific IgE per se does not permit a definitive conclusion concerning the response of effector cells to the respective allergen(s) and consecutive clinical symptoms in all patients. In an attempt to overcome this problem, a number of basophil-activation assays have been developed during the last few years. Today, allergen-induced activation of blood basophils can be employed as a specific and reliable measure of IgE-dependent responses in sensitized individuals. Using recombinant allergens and basophil-specific markers, these novel assays appear to serve as simple and useful tests in component-resolved diagnosis of type I allergies. In the current article, the biochemical, functional, and technical background of these basophil tests is discussed.

Allergens↗