Induced Histamine Release Research Articles

Sweat antigen induces histamine release from basophils of patients with cholinergic urticaria associated with atopic diathesis

We previously demonstrated that the semipurified human sweat antigen causes skin reactions and histamine release from basophils via specific IgE in patients with atopic dermatitis (AD). Patients with cholinergic urticaria (ChU) also develop skin reactions and histamine release of basophils in response to autologous sweat. To study whether or not patients with ChU share sensitivity for the sweat antigen with patients with AD and to study the clinical characteristics among patients with ChU and the relationship with histamine-release activity of basophils. The sweat antigen that induces histamine release from basophils of patients with AD was prepared by Con-A, anion-exchange and reverse-phase chromatography. Relationships between histamine-release activity against the sweat antigen and clinical features of patients with ChU were analysed. Twenty-three of 35 patients with ChU showed > 5% net histamine release in response to the semipurified sweat antigen, whereas none of healthy controls did so. In patients with ChU, histamine release in response to semipurified sweat antigen significantly correlated with the level of serum IgE and eosinophil numbers in peripheral blood. Incidence of each atopic disease in patients with ChU tended to be higher than in the general Japanese population. When the patients were categorized according to their responses in the histamine release test, the positive group tended to show a higher incidence of AD and bronchial asthma compared with the negative group. ChU and AD may share hypersensitivity to common antigens in sweat. The sweat allergy and atopic diathesis are associated with each other.

Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)-induced histamine release is enhanced with SHIP-1 knockdown in cultured human mast cell and basophil models

Previously, we demonstrated a negative correlation between histamine release to histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) and protein levels of SHIP-1 in human basophils. The present study was conducted to investigate whether suppressing SHIP-1 using small interfering (si)RNA technology would alter the releasability of culture-derived mast cells and basophils, as determined by HRF/TCTP histamine release. Frozen CD34+ cells were obtained from the Fred Hutchinson Cancer Research Center (Seattle, WA, USA). Cells were grown in StemPro-34 medium containing cytokines: mast cells with IL-6 and stem cell factor (100 ng/ml each) for 6-8 weeks and basophils with IL-3 (6.7 ng/ml) for 2-3 weeks. siRNA transfections were performed during Week 6 for mast cells and Week 2 for basophils with siRNA for SHIP-1 or a negative control siRNA. Changes in SHIP-1 expression were determined by Western blot. The functional knockdown was measured by HRF/TCTP-induced histamine release. siRNA knockdown of SHIP-1 in mast cells ranged from 31% to 82%, mean 65 +/- 12%, compared with control (n=4). Histamine release to HRF/TCTP was increased only slightly in two experiments. SHIP-1 knockdown in basophils ranged from 34% to 69%, mean 51.8 +/- 7% (n=4). Histamine release to HRF/TCTP in these basophils was dependent on the amount of SHIP knockdown. Mast cells and basophils derived from CD34+ precursor cells represent suitable models for transfection studies. Reducing SHIP-1 protein in cultured mast cells and in cultured basophils increases releasability of the cells.

Evaluation by double‐blind placebo‐controlled oral challenge of the clinical relevance of IgE antibodies against plant glycans

The clinical relevance of immunoglobulin E (IgE) to plant glycans is a longstanding debate. We sought to evaluate their clinical reactivity using the human glycoprotein lactoferrin expressed in rice. Allergic patients with IgE antibodies against plant glycans were analyzed for the presence of IgE against rice-produced lactoferrin. The potency of IgE to induce mediator release was assessed by basophil histamine release and skin prick tests (SPTs). Clinical relevance was evaluated by double-blind placebo-controlled oral challenge (DBPCOC). Twenty-four of 29 sera (82.7%) with IgE antibodies against plant glycans demonstrated IgE binding to transgenic lactoferrin. In three of five cases transgenic lactoferrin induced histamine release. Compared to a control major grass pollen allergen lactoferrin concentrations needed for biological activity of IgE were 5-6 orders of magnitude higher. Skin prick test and DBPCOC were negative in five patients with potential clinical reactivity that volunteered to undergo these in vivo challenges. Poor or no biological activity and lack of clinical relevance of IgE-binding plant glycans (five out of five) was demonstrated using human lactoferrin expressed in rice as a model.

Systemic administration of an Fcγ–Fcε-fusion protein in house dust mite sensitive nonhuman primates

Crosslinking FcεRI and FcγRIIB receptors inhibits mast cell and basophil activation, decreasing mediator release. In this study, a fusion protein incorporating human Fcγ and Fcε domains, hGE2, was shown to inhibit degranulation of human mast cells and basophils, and to exhibit efficacy in a nonhuman primate model of allergic asthma. hGE2 increased the provocative concentration of dust mite aeroallergen that induced an early phase asthmatic response. The treatment effect lasted up to 4 weeks and was associated with reduction in the number of circulating basophils and decreased expression of FcεRI on repopulating basophils. Repeat hGE2 dosing induced production of serum antibodies against human Fcγ and Fcε domains and acute anaphylaxis-like reactions. Immune serum induced histamine release from human IgE or hGE2-treated cord blood-derived mast cells and basophils in vitro. These results indicate that repeat administration with hGE2 induced an antibody response to the human molecule that resulted in activation rather than inhibition of allergic responses.

The effects of dasatinib on IgE receptor–dependent activation and histamine release in human basophils

AbstractDasatinib is a multitargeted drug that blocks several tyrosine kinases. Apart from its well-known antileukemic activity, the drug has attracted attention because of potential immunosuppressive and anti-inflammatory effects. We report that dasatinib at 1 μM completely blocks anti-IgE–induced histamine release in blood basophils in healthy donors, and allergen-induced release of histamine in sensitized individuals. In addition, dasatinib inhibited FcϵRI-mediated release of IL-4 and IgE-mediated up-regulation of CD13, CD63, CD164, and CD203c in basophils. The effects of dasatinib were dose-dependent (IC50: 50-500 nM) and specific for FcϵRI activation in that the drug failed to inhibit C5a-induced or Ca-ionophore–induced histamine release. Interestingly, at lower concentrations, dasatinib even promoted FcϵRI-dependent histamine release in basophils in allergic subjects. In consecutive studies, dasatinib was found to interact with and block several FcϵRI downstream targets in basophils, in-cluding Btk. Correspondingly, FcϵRI-mediated histamine secretion in basophils was markedly reduced in Btk knockout mice and in a patient with Btk deficiency. However, the remaining “low-level” mediator secretion in Btk-deficient cells was fully blocked down again by 1 μM dasatinib. Together, these data suggest that dasatinib inhibits FcϵRI-mediated activation of basophils through multiple signaling molecules including Btk. Dasatinib may be an interesting agent for immunologic disorders involving Btk-dependent responses or/and FcϵRI activation of basophils.

The relationship between human β-defensin 3 (hBD3) expression and mean histamine concentration in human placental tissue

Human defensins are small cationic, cysteine-rich peptides with a wide range of antimicrobial activities [1]. Human β-defensin-3 is widely expressed in placentae and exhibits antimicrobial activity against a number of human pathogens; multiresistant Gram-postitive Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, Gram-negative Pseudomonas aeruginosa and Escherichia coli and the yeast Candida albicans [1, 2]. When stimulated by bacterial infections and by interferon gamma, the amnion and placental cells produce hBD-3 [3]. Human placental tissue contains a moderate amount of histamine (HA) in vesicular structures in mast cells [4]. As hBD-3 induces HA release from mast cells, we examined the relationship between placental hBD3 expression and mean HA concentration in placental tissue in normal (N = 12; group II) and chorioamnionitis-complicated pregnancies (N = 12; group I) [5].

Induced Loss of Syk in Human Basophils by Non-IgE-Dependent Stimuli

In the general population, Syk expression in human basophils is highly variable and correlates well with the IgE-mediated responsiveness of these cells. Previous studies established that IgE-mediated stimulation results in loss of Syk expression. The current studies investigated whether stimulation through other receptors results in loss of Syk. Two classes of stimulation were examined, those that operate through the kinase Syk and those that operate through a GTP-binding protein. These studies demonstrated that aggregation of leukocyte Ig-like receptor LILRA-2 resulted in phosphorylation of Syk and c-Cbl, was inhibited by a third generation Syk inhibitor with an expected IC(50), and induced histamine release in strict proportion to release induced by anti-IgE Ab. Stimulation of LILRA-2 for 18 h resulted in modest loss of Syk that correlated with the more profound loss of Syk induced by anti-IgE Ab. Human recombinant histamine-releasing factor has also recently been shown to induce Syk phosphorylation and in the current studies has also been shown to induce loss of Syk in 18-h cultures. fMLP stimulation for 18 h was also found to induce modest loss of Syk. fMLP induced phosphorylation of c-Cbl that was sustained for at least 45 min. Phosphorylation of c-Cbl was inhibited by a Syk kinase inhibitor but with an IC(50) that was not consistent with Syk activity, suggesting another kinase was responsible for Cbl phosphorylation following fMLP. These studies demonstrate that it is possible to induce the loss of Syk expression in human basophils by a non-IgE-dependent mechanism and even by a mechanism that does directly involve Syk in the reaction complex.

Effects of human hair and nail proteins and their films on rat mast cells

Human hair and nail are valuable materials for producing individual corresponding biocompatible materials. A rapid and convenient protein extraction method (Shindai method) and novel procedures for preparing their protein films from their extracts have been developed using human hair and nail. The effects of the human hair and nail proteins and their films on histamine release from rat peritoneal mast cells were investigated. Both protein solutions and their films, mainly consisting of keratins and matrix proteins, did not induce histamine release from the mast cells. Scanning electron microscopy (SEM) also showed that the mast cells were only slightly affected by adding the human hair and nail proteins or by incubating on their protein films. The IgE-dependent histamine release was inhibited by the hair and nail proteins and their films. Incubation of the mast cells with the hair and nail proteins prior to the addition of the IgE serum resulted in a high inhibition (50%) of the histamine release, while the inhibition was approximately 10% when the protein solutions were mixed with the mast cells after incubation with the IgE serum. These results suggest that the human hair and nail proteins and their films will be useful materials for antiallergic actions.

Histamine enhances the production of human β-defensin-2 in human keratinocytes

The anti-microbial peptide human beta-defensin-2 (hBD-2), produced by epidermal keratinocytes, plays pivotal roles in anti-microbial defense, inflammatory dermatoses, and wound repair. hBD-2 induces histamine release from mast cells. We examined the in vitro effects of histamine on hBD-2 production in normal human keratinocytes. Histamine enhanced TNF-alpha- or IFN-gamma-induced hBD-2 secretion and mRNA expression. Histamine alone enhanced transcriptional activities of NF-kappaB and activator protein-1 (AP-1) and potentiated TNF-alpha-induced NF-kappaB and AP-1 activities or IFN-gamma-induced NF-kappaB and STAT1 activities. Antisense oligonucleotides against NF-kappaB components p50 and p65, AP-1 components c-Jun and c-Fos, or H1 antagonist pyrilamine suppressed hBD-2 production induced by histamine plus TNF-alpha or IFN-gamma. Antisense oligonucleotide against STAT1 only suppressed hBD-2 production induced by histamine plus IFN-gamma. Histamine induced serine phosphorylation of inhibitory NF-kappaBalpha (IkappaBalpha) alone or together with TNF-alpha or IFN-gamma. Histamine induced c-Fos mRNA expression alone or together with TNF-alpha, whereas it did not further increase c-Jun mRNA levels enhanced by TNF-alpha. Histamine induced serine phosphorylation of STAT1 alone or together with IFN-gamma, whereas it did not further enhance IFN-gamma-induced tyrosine phosphorylation of STAT1. The histamine-induced serine phosphorylation of STAT1 was suppressed by MAPKK (MEK) inhibitor PD98059. These results suggest that histamine stimulates H1 receptor and potentiates TNF-alpha- or IFN-gamma-induced hBD-2 production dependent on NF-kappaB, AP-1, or STAT1 in human keratinocytes. Histamine may potentiate anti-microbial defense, skin inflammation, and wound repair via the induction of hBD-2.

Novel clinical and serological aspects in non-allergic asthma

We have recently observed that skin reactivity to autologous serum injection is common in patients with non-allergic asthma. However, clinical significance of skin reactivity to autologous serum remains to be defined. To evaluate the possible relation between skin reactivity to autologous serum and clinical and laboratory characteristics in a series of patients with non-allergic asthma. Fifty-five patients with non-allergic asthma underwent in vivo autologous serum skin test (ASST) and in vitro basophil histamine release assay using basophils from a normal donor. Clinical and laboratory characteristics including peripheral blood eosinophilia, antinuclear antibodies and total IgE concentration were evaluated. As control, ASST was performed in 10 allergic asthmatic patients, 10 patients with allergic rhinitis and 10 normal subjects. ASST was positive in 29/55 non-allergic asthmatics (53%), whereas it was negative in all 30 control subjects (P<0.001). The sera of 6 out of 51 patients induced in vitro histamine release from autologous basophils. The sera from two patients induced histamine release from membrane IgE-stripped basophils. A significant predominance of female sex (83%) and a high incidence of antinuclear antibodies (ANA) positivity (55%) were found among ASST-positive patients. These findings indicate that ASST is positive in about half patients with non-allergic asthma and that a proportion of patients (16%) has functional evidence of circulating histamine-releasing factors. In addition, predominance of female sex and frequent ANA positivity are in line with an autoimmune basis of non-allergic asthma.

Aspergillus and Penicillium allergens: Focus on proteases

Penicillium and Aspergillus species are prevalent airborne fungi. It is imperative to identify and characterize their major allergens. Alkaline and/or vacuolar serine proteases are major allergens of several prevalent Penicillium and Aspergillus species. They are also major immunoglobulin (Ig) E-reacting components of the most prevalent airborne yeast, Rhodotorula mucilaginosa, and the most prevalent Cladosporium species, C. cladosporioides. IgE cross-reactivity has been detected among these major pan-fungal serine protease allergens. In addition, the alkaline serine protease of P. chrysogenum (Pen ch 13) induces histamine release from basophils of asthmatic patients, degrades the tight junction protein occludin, and stimulates release of proinflammatory mediators from human bronchial epithelial cells. In addition to induction of IgE and inflammatory airway responses, the alkaline serine protease allergen of A. fumigatus (Asp f 13) has synergistic effects on Asp f 2-induced immune response in mice. Studies of these serine protease major allergens elucidate the diverse allergic disease mechanisms and facilitate the development of better therapeutic strategies.

STI571 (Glivec®) affects histamine release and intracellular pH after alkalinisation in HMC‐1560, 816

The human mast cell line (HMC-1(560, 816)) was used to study the effect of the tyrosine kinase inhibitor STI571 (Glivec) on exocytosis, intracellular Ca(2+) and pH changes, because STI571 inhibits the proliferation of HMC-1(560) and induces its apoptosis. This drug does not have these effects on HMC-1(560, 816). Exocytosis in HMC-1(560, 816) cells can be stimulated by alkalinisation with NH(4)Cl as well as with ionomycin. Surprisingly 24-h pre-incubation with STI571 decreases spontaneous histamine release of HMC-1(560, 816) cells, but increases the histamine response after alkalinisation and not after ionomycin-stimulation. After addition of NH(4)Cl, pH(i) has a higher increase in STI571 pre-incubated cells, without changing intracellular Ca(2+) concentration. Activation of PKC in combination with tyrosine kinase inhibition increases also histamine release in HMC-1(560, 816) cells. Strangely, STI571 pre-incubated cells with PKC inhibited by rottlerin show the same effects. In these cells, cytosolic pH increases more than in control cells. This is the first report of STI571 effect in HMC-1(560, 816) cells. It seems that different pathways modulate signals for proliferation and exocytosis. STI571 does not only inhibit KIT TyrK, but may also influence cytosolic pH after alkalinisation in both cell lines, HMC-1(560) and HMC-1(560, 816), and this ends in induced histamine release. This work is important since HMC-1(560, 816) cells are reported in 80% of aggressive systemic mastocytosis cases and the understanding of some signalling pathways involved in mast cell response could facilitate drug targeting.

PGE2 suppresses excessive anti‐IgE induced cysteinyl leucotrienes production in mast cells of patients with aspirin exacerbated respiratory disease

Aspirin causes bronchospasm in patients with aspirin exacerbated respiratory disease (AERD). The contribution of mast cells to the increased cysteinyl-leucotrienes (cys-LTs) detected in AERD patients is however not defined. Effects of prostaglandin (PG) E(2) and inhibitors of cyclooxygenase (COX) and lipoxygenase (LO) pathways on mediator release from cultured mast cells of normal subjects, aspirin tolerant asthma (ATA) and AERD patients were compared to better define the role of mast cells in AERD. Mast cells were cultured from peripheral blood progenitors and were activated by anti-IgE. Histamine, PGD(2) and cys-LTs released were then determined. Basal release of all three mediators was similar in all subjects. Although the release of all three mediators was increased by anti-IgE, mast cells from AERD patients produced significantly more cys-LTs (6.9 +/- 2.0 ng/10(6) cells) than normal and ATA subjects (2.3 +/- 0.8 and 1.7 +/- 0.5 ng/10(6) cells, respectively). While COX and LO pathway inhibitors did not affect anti-IgE induced histamine release, they significantly suppressed the production of PGD(2) and cys-LTs, respectively, in all patients. PGE(2) significantly enhanced anti-IgE induced histamine and PGD(2) release from mast cells of normal subjects but not those of ATA and AERD patients. In contrast, PGE(2) suppressed only anti-IgE induced cys-LTs release from mast cells of AERD patients. We speculate that overproduction of cys-LTs is unique to mast cells of AERD patients and is particularly sensitive to suppression by PGE(2). Consequently reduction of PGE(2) production by aspirin removes this endogenous control of cys-LTs overproduction, resulting in asthma attack.

Influence of UVB, UVA and UVA1 Irradiation on Histamine Release from Human Basophils and Mast Cells In Vitro in the Presence and Absence of Antioxidants ¶

UV irradiation is widely used for the treatment of atopic eczema. In recent years, UVA1 phototherapy has gained increasing attention. This study analyzed the influence of different UV wavelengths—especially UVA1—on histamine release from human basophils and mast cells. The modulation of this parameter might be responsible for some of the therapeutic effects of UV irradiation. Enriched human basophils and human mast cells (HMC1 cell line) were irradiated with increasing doses of UVB, UVA and UVA1 in vitro. After irradiation, different stimulants were added to induce histamine release. In additional experiments, basophils were preincubated with superoxide dismutase, ascorbate or trolox to study the role of antioxidants in the modulation of histamine release after UV irradiation. UVA and UVA1 significantly inhibited histamine release from basophils and mast cells. UVB only had an inhibitory effect on mast cells. Preincubation with superoxide dismutase and ascorbate did not influence the inhibitory effect of UVA1 on basophil histamine release, whereas trolox decreased significantly the histamine release from nonirradiated basophils.

Isolation and characterization of native Cry j 3 from Japanese cedar (Cryptomeria japonica) pollen

Japanese cedar (Cryptomeria japonica) pollinosis is the most prevalent allergy in Japan. Recently, the Japanese cedar pollen allergen Cry j 3 was cloned as a homologue of Jun a 3, which is a major allergen from mountain cedar (Juniperus ashei) pollen. However, native Cry j 3 has not been isolated and there are no reports on its allergenic activity. The aims of this study were to isolate native Cry j 3 and assess its immunoglobulin E (IgE)-binding capacity in patients with Japanese cedar pollinosis. Native Cry j 3 was purified from Japanese cedar pollen by multidimensional chromatography. We assessed the IgE-binding capacity using sera from patients allergic to Japanese cedar pollen by immunoblot analysis and ELISA. Moreover, we assayed the capacity of Cry j 3 to induce histamine release from the patients' leukocytes. We cloned cDNA corresponding to purified Cry j 3 from a cDNA library of Japanese cedar pollen. We isolated native Cry j 3 as a 27-kDa protein. The IgE-binding frequency of Cry j 3 from the sera of patients allergic to Japanese cedar pollen was estimated as 27% (27/100) by ELISA. Cry j 3 induced the release of histamine from leukocytes. We cloned the cDNA and named it Cry j 3.8. Cry j 3.8 cDNA encoded 225 amino acids and had significant homology with thaumatin-like proteins. Cry j 3 is a causative allergen in Japanese cedar pollinosis and may play crucial roles in the cross-reactivity with oral allergy syndrome.

Changes in syk expression in human basophils (HB) induced by a non-IgE-dependent receptor, LIR7 (38.9)

Abstract Expression of syk in HB is highly variable among subjects and correlates with the ability of the cell to respond to FceRI aggregation. Because evidence suggests a post-translational influence on syk expression, we sought ways that syk could be down-regulated by the activation of non-IgE-dependent receptors. HB express LIR7 and aggregation of LIR7 induces mediator secretion kinetically similar to IgE-mediated release. These studies test whether aggregation of LIR7 reduces expression of syk and whether LIR7 operates through syk to induce histamine release (HR). HB were stimulated with mouse anti-LIR7 and anti-mouse Ab (the combination abbreviated to: aLIR7) and assessed for syk phosphorylation and for changes in syk expression. HR was examined ± the presence of a third generation syk inhibitor. aLIR7 induced syk phosphorylation and a modest loss of syk in 18 hour cultures (14±5% loss, n=11, p=0.013) compared to anti-IgE (53±10% loss). There was a correlation between the amount of syk loss induced by anti-IgE and the loss induced by aLIR7 (r=0.63). There was a correlation, r=0.97, between HR induced by anti-IgE and that induced by aLIR7 (means= 43%&amp;25%). The IC50 for inhibition of aLIR7-induced HR was 0.2 μM (IC50 for anti-IgE was 0.038 μM). Each of these data sets is consistent with a dependence of LIR7 signaling on syk and shows that a non-IgE-dependent stimulus can alter syk expression levels. Supported NIH-AI20253

The Effect of H1 Antagonists Carebastine and Olopatadine on Histamine Induced Expression of CC Chemokines in Cultured Human Nasal Epithelial Cells

CC chemokines have been shown to play an important role in inducing selective recruitment of inflammatory cells into local allergic inflammatory sites. CC chemokines are also known as histamine releasing factors. We previously showed that histamine enhances transcription of CC chemokines from nasal mucosa which leads to further induction of histamine release. This cyclic cascade may cause prolonged allergic inflammation. The aim of this study is to clarify the relationship between histamine and CC chemokine production by using human nasal epithelial cells (HNECs) and to examine the potential of H1 receptor (H1R) antagonists in new therapeutic approaches for the treatment of nasal allergy. HNECs were isolated from the nasal turbinates of patients diagnosed with nasal allergy. HNEC monolayers were cultured for 48 hours with or without histamine (10(-3) to 10(-5) mol/L). Furthermore, an H1R antagonist, either carebastine or olopatadine, was added to the supernatant (10(-3) to 10(-7) mol/L) 30 minutes before incubation with histamine. The expression of Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) in the culture media were measured by ELISA. The release of RANTES and MCP-1 was significantly upregulated by histamine compared with the control group. Both carebastine and olopatadine inhibited the release of CC chemokine production to the control level in both groups. This study suggests that the interaction between histamine and CC chemokines may prolong allergic inflammation in human nasal mucosa. We also demonstrate the potential use of H1R antagonists in new therapeutic approaches to the treatment of nasal allergy through inhibiting this histamine-CC chemokine interaction.

Human recombinant Histamine Releasing Factor (HrHRF) Induced Histamine Release (HR) is Associated with SHIP Knockdown (k/d) in both the Cultured Human Mast Cell (MC) and Basophil Models

Human recombinant Histamine Releasing Factor (HrHRF) Induced Histamine Release (HR) is Associated with SHIP Knockdown (k/d) in both the Cultured Human Mast Cell (MC) and Basophil Models

Measurement of Hemodynamic Changes Caused by Administration of Atracurium Besylate after Pretreatment with Anti-histamine Agent

Background: Hemodynamic changes through the histamine-induced release of atracurium are relatively common, but can be particularly dangerous in hemodynamically unstable patients. This study evaluated the effectiveness of a pretreatment with an anti-histamine agent before the administration of atracurium in the prevention of histamine-induced hemodynamic changes. Methods: Forty-eight ASA class I and II patients were assigned to four groups. Groups 1 and 2 were assigned to receive atracurium through a bolus 0.5 mg/kg. Groups 3 and 4 were assigned to receive atracurium through a bolus 1.0 mg/kg. Group 1 and 3 were pretreated with pheniramine (H1-blocker) and ranitidine (H2-blocker) intravenously before the induction of general anesthesia. After induction, Hemosonic TM 100 was installed and the following hemodynamic parameters were measured: systemic vascular resistance (SVR), cardiac index (CI), heart rate (HR) and blood pressure (BP) immediately before, 1, 2, 3, 5 and 10 min after the rapid administration of the atracurium bolus befo re the skin incision. Results: Groups 1 and 3 showed more stable hemodynamics than groups 2 and 4. Group 2 showed more significant changes in the SVR, CI, BP, HR than group 1 (P ＜ 0.05). Group 4 showed more significant changes in the SVR, CI, BP, HR than group 3, and some cases were significant hemodynamically (P ＜ 0.05). Group 4 showed more significant changes in the SVR, CI, BP, HR than group 2 (P ＜ 0.05). Conclusions: Pretreatment with an anti-histamine drug prior to the administration of atracurium can be effective in attenuating

L3L4ES antigen and secretagogues induce histamine release from porcine peripheral blood basophils after Ascaris suum infection

The aim of this paper was to investigate the role of porcine basophils in protective immunity. Experimental pigs were infected with 10(3) Ascaris suum eggs daily for 21 days. Control pigs were maintained helminth-free. Circulating porcine basophils were isolated from the anticoagulated whole blood of A. suum-infected and noninfected pigs by dextran (4.5%) sedimentation of erythrocytes or by the centrifugation of dextran-isolated leukocytes through discontinuous Percoll gradients. Results showed that 2.2% of the isolated leukocytes, stained with May-Grunwald Giemsa, were basophils. Each basophil from infected pigs contained 1.30 x 10(-2) to 1.20 x 10(-1) pg of histamine. Peripheral blood basophils (PBBs) from infected swine released 49% specific histamine when induced with A. suum-derived antigen (L3L4ES), 55% with anti-immunoglobulin G, and 62% with calcium ionophore A23l87. During A. suum infection, the number of isolated basophils and histamine levels peaked at 14 to 21 days postinfection and then showed a significant decrease. Percent-specific histamine released from PBBs by infected swine was significantly greater than that released by control pigs. The L3L4ES antigen and secretagogues effectively induced specific/nonspecific histamine release from PBBs and should facilitate future investigations of porcine basophils.