The effect of nicotine on basophil histamine release

Background:Changes in the immune and inflammatory response are induced by smoking tobacco but underlying mechanisms remain to be elucidated.Objective:This study investigated the effect of nicotine agonists on histamine release from human basophils.Methods:Peripheral blood basophils were obtained from healthy volunteers. The effect of the nictotine agonists [–]-1-methyl-2-[3-pyridyl]pyrrolidine and (+)-nicotine di-p-toluoyltartrate salt on cell viability and anti-IgE induced histamine release was investigated.Results:Cell viability was not altered by preincubation with the agents for 15 min. Anti-IgE induced histamine release was significantly inhibited by preincubation (15 min, 37°C) with [–]-1-methyl-2-[3-pyridyl]pyrrolidine at the highest concentration tested 10^–3 M (p<0.01). Preincubation (15 min, 37°C) with (+)-nicotine di-p-toluoyltartrate salt significantly inhibited anti-IgE induced histamine release at 10^–3M and 10^–5 M (p<0.05).Conclusions:This study has demonstrated that nicotine agonists inhibit histamine release from human basophils. Further studies examining the effect of smoking on basophil activation are required.Received 28 September 2003; returned for revision 1 December 2003; accepted by A. Falus 23 December 2003     

The basophil activation test in the diagnosis of immediate drug hypersensitivity

Hypersensitivity reactions to drugs account for 15% of all adverse drug reactions and represent an important health problem with significant morbidity and mortality. This article describes the current applications and perspectives of the basophil activation test by flow cytometry in the diagnosis of immediate-type drug allergy, with particular focus on its diagnostic performance in allergy to neuromuscular blocking agents, antibiotics and NSAIDs and on future applications.     

Human basophil releasability. I. Age-related changes in basophil releasability

Releasability of human basophils (i.e., the response to a standard stimulus) is an important parameter in several pathophysiologic conditions. We studied the IgE (anti-IgE)- and non-IgE-mediated (f-met peptide and Ca2+ ionophore A23187) releasability of human basophils obtained from 63 normal donors whose ages ranged from 1 to 86 years. The maximum percent of histamine release induced by anti-IgE was significantly correlated (rs = 0.57; p less than 0.001) with the age of donors. The sensitivity to a standard concentration of anti-IgE (3 X 10(-2) mcg/ml) was also correlated with the age of cell donors (rs = 0.68; p less than 0.001). In the population of 63 donors tested, the maximum percent of histamine release and the cell sensitivity to anti-IgE appeared to be independent of the serum concentration of IgE. However, we found a positive correlation (rs = 0.55; p less than 0.05) between serum IgE level and anti-IgE-induced histamine release in the group less than 20 years of age. In contrast, a negative correlation (rs = -0.32; p less than 0.05) between serum IgE level and anti-IgE-induced histamine secretion was found in the group greater than 21 years of age. The maximum percent of histamine release induced by f-met peptide and Ca2+ ionophore A23187 appeared to be independent to both the age of the donors and the serum IgE level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dexamethasone inhibits basophil migration

Glucocorticoids have been shown to inhibit the local accumulation of basophils during the allergen-induced late-phase reaction (LPR). Since migration is an essential step in the recruitment of basophils from the circulation, we examined whether the widely used glucocorticoid, dexamethasone (DEX), directly acts on basophils to inhibit the migration caused by C5a, interleukin (IL)-3, and IL-8. When purified basophils were preincubated with various concentrations of DEX, a dose-dependent inhibition was observed; DEX at concentrations as low as 1 nM reduced the number of migrated basophils by 30–40 %; at higher concentrations, it showed a slightly stronger inhibitory effect. There was no significant difference in the effect of DEX on the migration caused by the three chemoattractants. The action of DEX took place rapidly; apparent inhibition was observed even when migration was initiated without preincubation. Although the inhibitory effect of this agent was not reversed when DEX was removed by washing, the inhibition was not mediated by the toxicity as measured by the trypan-blue exclusion test. These results indicate that the in vivo blocking effect of glucocorticoids on basophil accumulation during LPR is mediated in part by direct action to inhibit the migration of basophils.     

Chemotaxis of human basophil leucocytes

Human peripheral blood basophils from two patients with unusually high basophil counts in association with chronic myelogenous leukaemia migrated in vitro toward various chemotactic agents of human origin. These included supernatants from sensitized lymphocytes challenged with specific antigen, diffusates from lung fragments challenged with pollen antigen E, the enzyme plasma kallikrein, and two complement derived agents, C5a and C[unk][unk][unk]. Thus, chemotaxis in vitro, a previously unreported property of human basophils, has been observed, although none of the agents tested produced a selective chemotactic response.     

Glucocorticoids induce basophil apoptosis

BACKGROUND: Induction of apoptosis represents an important mechanism by which glucocorticoids (GCCs) exert their anti-inflammatory properties. The effects of GCCs on apoptosis have been determined in various immune cells and found to vary among different cell types. On the other hand, the effects of GCCs on apoptosis of basophils, active participants in allergic inflammation, have remained obscure. OBJECTIVE: The objective of this study was to investigate the effects of GCCs on basophil apoptosis. METHODS: Basophils were highly purified (purity, >97%) by Percoll density gradient centrifugation followed by negative selection. Cell status was determined by their ability to bind annexin V and exclude propidium iodide. DNA fragmentation was determined by flow cytometry. RESULTS: Dexamethasone (DEX) significantly accelerated the decrease in live cells and increased the number of apoptotic cells in a time-dependent fashion. Light microscopy as well as DNA fragmentation assay confirmed the induction of apoptosis by DEX. A half-maximal effect was observed in a DEX concentration range from 10(-9) to 10(-8) mol/L. Sex steroids did not induce basophil apoptosis at all. DEX also induced basophil apoptosis in the presence of low doses of IL-3. CONCLUSION: GCCs exert potent apoptogenic effects on basophils. GCC-mediated apoptogenic effects on basophils might have implications with respect to the mechanism of action of this class of drugs in allergic disorders.     

The return to sleep.

Six young adult subjects were awakened five to eight times per night from stage 2 sleep in a standardized manner for a series of at least 11 non-consecutive nights. After adaptation to the procedure, subjects received placebo, pentobarbital, or flurazepam on two random nights and caffeine on one night. The latency of the return to sleep after each awakening was measured. On placebo nights a characteristic U-shaped curve of latency as a function of time of night was found. Latencies were long shortly after sleep onset but decreased rapidly to about 50 sec before beginning an approximately linear logarithmic increase throughout the rest of the night. The drugs characteristically altered this time course. Pentobarbital decreased latencies in the first half of the night. Flurazepam decreased latencies throughout the night. Caffeine increased latencies during the first half of the night.     

Non-IgG1 nature of cutaneous basophil hypersensitivity factor in contact sensitivity. II. Demonstration of antigen-dependent basophil chemotactic activity of cutaneous basophil hypersensitivity factor

It was recently demonstrated that there was a specific activity to induce basophil-rich skin reaction in the sera of contact-sensitized guinea pigs (CBH factor, CBH-F). In the in vitro chemotactic assay system, CBH-F was shown to have weak basophil chemotactic activity but enhanced its activity in the presence of corresponding antigen(s). Furthermore, basophil chemotaxis in reaction to the antigen(s) was observed when the cells were preincubated with CBH-F. It worked mainly for Percoll-separated bone marrow basophils but not for oil-induced peritoneal macrophages. Immunological analysis revealed that CBH-F was a protein with a small molecular weight (MW 4-6 X 10(4] with an antigen binding site and isoelectric point of between 4.5 and 5.0. It did not show any characteristics of IgG1 or IgG2 on immunoadsorbent column and immunoelectrophoresis. Enzyme treatment with insoluble trypsin eliminated the chemotactic activity but this was not the case with neuraminidase treatment.