Biomedical subjects

B Lebel

Publications and source records attributed to B Lebel.

At least 37 records · Page 2Linked to original sources

PubMed1994

Aggregated IgE mimic interleukin-3-induced histamine synthesis by murine hematopoietic progenitors.

Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by inducing histamine production. This effect does not result from degranulation of histamine-containing cells, but from histamine synthesis, as assessed by the following findings. (1) The histamine content of freshly isolated bone marrow cells is too low to account for the increase in extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine production in the presence of the specific inhibitor of histidine decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic activity and the mRNA expression of HDC were enhanced in response to IL-3 or IgE. Artificial aggregation or formation of IgE immune complexes augmented ther effect on histamine synthesis, indicating that the aggregated form is responsible for this biologic activity. Yet, it is apparently not mediated by Fc epsilon RI because their cross-linkage by dinitrophenyl bovine serum albumin after presensitization with IgE did not induce histamine production by hematopoietic progenitors. Among other aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a consistent but lower effect, whereas IgM and IgA were completely inactive. The target cells of IL-3 and IgE in terms of histamine synthesis do not belong to mature bone marrow populations, especially mast cells. They copurify with hematopoietic progenitors in the low-density layers of a discontinuous Ficoll gradient where they represent around 5% of the cells, as determined by in situ hybridization. This percentage remained the same, regardless of whether the cells were stimulated by IgE or IL-3 alone or by a combination of both, suggesting a common responder cell. In accordance with this notion, histamine-producing cells could not be distinguished from each other on the basis of density, size and internal structure, or rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect of IgE.

Animals↗

PubMed1993

Interleukin 3 promotes histamine synthesis in hematopoietic progenitors by increasing histidine decarboxylase mRNA expression.

Interleukin 3 (IL-3) is a potent stimulator of histamine production by cells from murine hematopoietic organs. We demonstrate herein that this phenomenon results from increased histidine decarboxylase (HDC: EC 4.1.1.22) activity in progenitor-enriched bone marrow cells (around 5% of the total bone marrow) isolated from the low density layers of a discontinuous Ficoll gradient. HDC levels are markedly enhanced after a 24 h incubation with IL-3 while a 4 h exposure results only in a slight activation. It results from increased expression of the mRNA coding for HDC, as assessed by Northern blot analysis after a 24 h incubation with IL-3. At the same time point and after a 4 h stimulation, we have evaluated the percentage of cells in this population which express HDC mRNA in response to IL-3, using in situ hybridization with the antisense riboprobe. We have thus established that enhanced HDC mRNA expression occurs in a small immature subset representing from 5 to 8% of the progenitor-enriched bone marrow cells.

Animals↗

PubMed1993

[Study of histidine decarboxylase activity (HDC) in murine fetal hematopoietic organs. Description of basophil-enriched splenic cell population during fetal life].

The role of histamine in vitro during hematopoiesis has been described by several authors. This work was carried out to determine whether histamine could be available in hemopoietic organs by measuring the HDC activity and the histamine content of developing hemopoietic tissues from C 57 BL/6 mice during fetal life (liver from the 12th day of gestation, spleen from the 14th day, and bone-marrow from the 17th day) and postnatal life. High values were found in the liver, the bone marrow, and especially the spleen between the 17th and the 19th days of gestation. A rapid fall in these values was seen near birth. Interestingly, electron microscopy analysis of day 18 fetal spleen cells, provides evidence for a basophil-rich cell population (25%).

Animals↗

PubMed1991

Differences in clinical and immunologic reactivity of patients allergic to grass pollens and to multiple-pollen species. II. Efficacy of a double-blind, placebo-controlled, specific immunotherapy with standardized extracts.

The IgE response of patients only allergic to grass pollens differs from response of patients allergic to multiple-pollen species. The IgE immunoblots to orchard-grass pollens confirmed that polysensitized patients had more proteins revealed than patients only allergic to grass pollens. To determine if both groups of patients present a different response toward specific immunotherapy (IT), a double-blind, placebo-controlled study was performed in 70 patients. Patients receiving the active treatment had a rush IT with either a standardized orchard grass-pollen extract or with a standardized mixed-pollen extract prepared, depending on the sensitivity of the patients. The maintenance dose was defined as that dose effective in grass-pollen IT in previous experiments. The same equipotent maintenance dose was administered for all pollen species. Symptom-medication scores during the pollen season and nasal challenge with orchard grass-pollen grains demonstrated that grass pollen-allergic patients had a significantly improved efficacy by comparison to placebo treatment, whereas polysensitized patients had a nonsignificant improvement. Serum grass-pollen IgG was significantly increased after IT in both treated groups. This study demonstrate that the response toward specific IT differs in patients only allergic to grass pollens by comparison to polysensitized patients.

Adolescent↗

PubMed1991

Clinical and immunologic reactivity of patients allergic to grass pollens and to multiple pollen species. I. Clinical and immunologic characteristics.

The heterogeneity of pollen-allergic individuals is well-known but poorly characterized. Twenty-six patients were studied to characterize their immunologic and clinical patterns. Thirteen patients were allergic only to grass pollens, and 13 other patients were allergic to grass-pollen and other pollen species, including Cupressaceae, plane tree, olive, and Parietaria. The IgE response was assessed by the titration of serum total IgE and orchard grass-specific IgE, as well as by IgE immunoblots to orchard-grass pollens. Clinical reactivity was assessed by nasal challenge with orchard-grass pollens before the pollen season and nasal and bronchial symptom-medication scores between April 1 and June 15. Pollen counts were obtained during this period of survey. Polysensitized patients had significantly increased levels of serum total and specific IgE and a greater heterogeneity of IgE immunoblots, suggesting an enhanced qualitative and quantitative IgE immune response. Polysensitized patients had nasal and bronchial symptoms occurring earlier than grass pollen-allergic individuals, confirming the priming effect caused by other plans flowering with an earlier season for both nasal and bronchial mucosa. Alternatively, the early symptoms may be attributable to the tree pollens or might reflect the higher grass-pollen IgE level in the polysensitized group. Bronchial symptoms appeared a few weeks after nasal symptoms. Nasal challenges were similar in both groups, and the severity of nasal symptoms during the season was not significantly different in both groups, suggesting that the intensity of symptoms is not related to the sensitization nor to the IgE immune response of the subjects.

Adolescent↗

PubMed1990

Antigenic challenge of immunized mice induces endogeneous production of IL-3 that increases histamine synthesis in hematopoietic organs.

Antigenic challenge of Nippostrongylus brasiliensis-infected mice induces a striking increase in histidine decarboxylase (HDC) activity in both spleen and bone marrow cells. This enhancement takes place within 1 h after injection, with a maximum at 4 h and a return to pretreatment values 20 h later. It is associated with the appearance of IL-3 in the sera of these mice. In addition, the intracellular histamine content in both hematopoietic organs is concomitantly increased. A similar injection of worm Ag into normal mice has no significant effect. Comparable enhancement of HDC activity and intracellular histamine content with almost identical kinetics is promoted by i.v. injection of rIL-3 into normal mice. Moreover, HDC levels in infected mice are increased to the same extent in response to either specific antigen or rIL-3 injection. Taken together these results support the conclusion that antigenic challenge of immunized mice induces endogeneous IL-3 which, in turn, promotes a rapid increase in histamine synthesis in hematopoietic organs.

Animals↗

PubMed1990

Interleukin 3 induces histamine synthesis in the human hemopoietic system.

Recombinant human interleukin 3 (rhIL-3) induces an increase in histamine production by human bone marrow, fetal liver, and cord blood cells. This phenomenon, already significant after 3 days of incubation, is strikingly enhanced following either enrichment in immature cell subpopulations or CD8+ cell depletion. It results from an increase in histamine synthesis because of 1) the low level of histamine cell content before any incubation, 2) the parallel increase in both extra- and intracellular histamine levels in response to rhIL-3, and 3) the early IL-3-induced increase in L-histidine decarboxylase (HDC; EC 4.1.1.22) activity. Moreover, rhIL-3 has no similar activity on adult peripheral blood cells, suggesting that it might be specific to the hemopoietic system.

Adult↗

PubMed1988

Correlation between symptoms and the threshold for release of mediators in nasal secretions during nasal challenge with grass-pollen grains.

Nasal challenges with pollen grains represent one of the techniques of provocation. However, the clinical criteria of positivity are not clearly established. Nasal challenges with increasing numbers of orchard-grass pollen grains were performed in 60 patients allergic to grass pollens and 20 normal subjects. Before any challenge, the nose was washed three times with saline and then lactose, and 50, 150, 450, 1350, and 4050 orchard-grass pollen grains were insufflated into the nostrils until a symptom score of 5 was reached. This score was mainly based on major symptoms of allergic rhinitis, for example, rhinorrhea, nasal obstruction, sneezes, and to a lesser extent, on minor symptoms, such as pruritus, conjunctivitis, and pharyngitis. Nasal secretions were obtained after each challenge by lavage. Histamine was titrated by a radioimmunoassay with a monoclonal antibody against acylated histamine. Prostaglandin D2 (PGD2) was assayed with an enzyme immunoassay with a polyclonal antibody against PGD2 methoxamine. None of the normal subjects had a symptom score greater than 2; 55/60 patients had a positive challenge. The release of PGD2 was significantly (p less than 0.001, Kruskal-Wallis test) correlated with a symptom score of 5; 74.5% of patients had a significant release of PGD2 in nasal secretions. In contrast, although 58.2% of patients had a release of histamine in nasal secretions when the challenge was positive, the correlation with symptom scores was not significant. PGD2 in nasal secretions increased 3.7-fold after a positive nasal challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1988

Antiallergic activity of H1-receptor antagonists assessed by nasal challenge.

Most oral drugs used for the treatment of allergic rhinitis are classified as H1-receptor antagonists, and although they represent major sales throughout the world, their mechanism of action is still poorly known. In an attempt to understand better the in vivo therapeutic effects of these drugs, a double-blind, crossover study was carried out. The study compared the effects of terfenadine and loratadine, nonsedative H1-receptor antagonists, on the immediate allergic response of the upper airways to challenge with orchard-grass pollens in 14 highly allergic subjects. Increasing numbers of pollen grains were insufflated into the nostrils, and the response of the subjects was assessed by examining symptoms and measuring the release of histamine and prostaglandin D2 in nasal secretions. Each drug was administered for a week before challenge. This study demonstrated the clinical efficacy of both drugs by comparison to that of a control day, since symptoms were observed for a significantly (p = 0.014) greater number of pollen grains. Only one patient had a significant release of histamine when they were treated with loratadine versus 10 during control day (p less than 0.0023) and six when they were treated with terfenadine (p less than 0.01). Prostaglandin D2 release occurred with a higher allergen dose when patients were treated with both drugs. This study indicates that some H1 antagonists also possess antiallergic activities.

Adult↗

PubMed1988

Spontaneous and non-specific release of histamine and PGD2 by bronchoalveolar lavage cells from asthmatic and normal subjects: effect of nedocromil sodium.

Mast cells have been implicated in the pathogenesis of allergic asthma but their role in non-allergic asthma remains to be elucidated. The spontaneous and non-specific release of histamine by suboptimal doses of calcium ionophore A23187 was studied in bronchoalveolar lavage cells obtained from nine asthmatic and seven healthy individuals. Bronchoalveolar lavage was performed with saline, and total cells were incubated without any secretagogue (spontaneous histamine release) or after addition of 1.25, 2.5 and 5 microM of A23187 for 30 min (net maximal release). Histamine was titrated by using a very sensitive radioimmunoassay using a monoclonal antibody against acylated histamine. The spontaneous release was similar in asthmatic (20.6 +/- 8.2%) and healthy individuals (17.4 +/- 8.4%). The net maximal release of histamine was significantly greater in asthmatic patients (28.1 +/- 17.4%) than in normal subjects (10.3 +/- 8.9%). The release of histamine was significantly correlated to the release of PGD2 measured by enzyme immunoassay using a polyclonal antibody against methoxamine-PGD2 (Spearman rank test: 0.78, P less than 0.01). In eight subjects, the release of histamine by A23187 was studied in the presence of nedocromil sodium and it was observed that this drug significantly (P less than 0.05) decreased the net maximal release of histamine. This study shows that mast cells from asthmatic individuals have a greater releasability than those of normal subjects.

Adult↗

PubMed1987

Nasal challenge with pollen grains, skin-prick tests and specific IgE in patients with grass pollen allergy.

Nasal challenges with pollen grains are as close as possible to natural pollen exposure, but they are not well documented in grass pollen allergy. Forty-four grass pollen allergic patients and ten non-allergic volunteers were tested by means of nasal challenge, quantitative skin-prick tests with a standardized orchard grass pollen extract and serum-specific IgE. Nasal challenges were performed with lactose and increasing concentrations of orchard grass pollen grains (15-3645 grains, three-fold increase). The test was considered to be positive when a symptom score over 5 was obtained, since this score had been previously correlated with the release of PGD2 in nasal secretions. All control subjects and 3/44 patients had a negative challenge. The number of orchard pollen grains required to elicit a positive challenge was 332 +/- 440 (range: 15-1215 grains) and the distribution was Gaussian. This number is higher than expected according to pollen calendars performed during the season, but owing to the priming effect of the nasal mucosa by allergens it is compatible to natural exposure. The correlation between nasal provocation tests and skin-prick test end-points was significant (P less than 0.005, Spearman rank test). Conversely there was no correlation between nasal challenge or skin-prick test end-point and serum-specific IgE.

Adolescent↗

PubMed1986

Histamine-producing cell stimulating factor (HCSF) and interleukin 3 (IL 3): evidence for two distinct molecular entities.

Because homogeneously purified interleukin 3 (IL 3) can induce an increase in histamine synthesis by normal bone marrow cells like histamine-producing cell stimulating Factor (HCSF), it has been suggested that HCSF and IL 3 might be identical. In this paper, we provide evidence that HCSF activity can be obtained without IL 3 activity (determined by the proliferation of an IL 3-dependent cell line). This distinction between HCSF and IL 3 has been achieved in three different ways: a) biochemical separation of HCSF from IL 3 in crude secondary MLC supernatants with description of different physicochemical characteristics of the two molecules; b) demonstration of an HCSF activity devoid of IL 3 activity in P388D1 conditioned medium, with the same characteristics as HCSF produced during secondary MLC but different from WEHI-3-derived HCSF activity resulting from IL 3; c) demonstration of a lack of inhibition of HCSF-induced histamine synthesis by anti-IL 3 immunoglobulins that clearly diminish IL 3-induced histamine production. These results demonstrate that two distinct factors (IL 3 and HCSF) promote histamine synthesis, but that IL 3 has more general effects on hemopoietic cells, whereas HCSF seems to be restricted to histamine-producing cells.

Animals↗

PubMed1985

[Is the histamine-producing cell stimulating factor (HCSF) identical to interleukin 3 (IL-3)?].

Since homogeneously purified Interleukin 3 can induce an increase in histamine synthesis by normal bone marrow cells (HCSF activity), it has been suggested that HCSF and IL3 could be identical. In this paper, we show evidence that HCSF activity can be obtained without any IL3 activity (determined by the proliferation of an IL3-dependent cell line). This distinction has been achieved in two different ways: (a) the physico-chemical separation of HCSF and IL3 from crude secondary MLC supernatants and (b) the spontaneous production by the P388D1 cell line of a factor possessing all the characteristics of HCSF without any IL3 activity. In addition, preliminary results show that anti-IL3 antibodies do not inhibit the increase in histamine synthesis induced by HCSF while it strongly diminishes that induced by IL3.

Animals↗

PubMed1984

Tests for allergy to housedust.

In an attempt to find a satisfactory combination of method and antigen extract for tests of hypersensitivity to housedust, variations of skin test, RAST, histamine release and basophil degranulation tests have been used to test efficacy of five commonly used extracts of housedust or its components. The Lincoln Multitest for skin prick tests in its present form induced too much trauma for type-I hypersensitivity tests, though it has advantages for comparison of several extracts. Histamine release and two versions of basophil degranulation tests all gave good results but not consistently. RAST gave the best correlation between all extracts, but neither the in vivo nor in vitro tests gave perfect concordance with sensitivity in all patients and all extracts.

Adult↗

PubMed1983

In vitro and in vivo histamine-producing cell-stimulating factor (or IL3) production during Nippostrongylus brasiliensis infection: coincidence with self-cure phenomenon.

Spleen cells from Nippostrongylus brasiliensis-infected mice produce large amounts of histamine in response to adult worm antigen. This phenomenon results from the production of HCSF (histamine-producing cell-stimulating factor, probably related to IL3) by sensitized lymphocytes. This factor acts on its target cells (presumably mast cell precursors) by inducing a rapid increase in histamine synthesis. Similarly, parasite infection generates enhanced histamine production by spleen cells in response to concanavalin A (Con A). This results from increases in both HCSF production and the HCSF sensitivity of its target cells. In all cases, maximal histamine and HCSF productions are obtained on day 8 after infection and coincide with parasite rejection. Methyl prednisolone suppresses HCSF production by infected mouse spleen cells in response to worm antigen or Con A. HCSF activity is found in vivo on day 8 in the sera of infected mice, 4 h after they are challenged with an i.v. injection of adult worm antigen. No activity is detected in the sera of normal mice with or without antigen injection. Sera from infected mice that did not receive the antigen exhibit a slight HCSF activity on day 8. Our data bring the first evidence of the existence of an in vivo production of HCSF.

Animals↗

PubMed1983

A high-sampling-rate automated continuous-flow fluorometric technique for the analysis of nanogram levels of histamine in biological samples.

An automated continuous-flow technique of the modified fluorometric method of Shore was devised to obtain a high sampling rate (60/h) and a sensitive measurement of the histamine content of biological samples. The volumes of samples range from 50 to 500 microliter. A linear relationship is obtained from 0 to 5 micrograms/ml (histamine base) with a good specificity. The limit of detection is 25 pg (actual amount). The coefficient of variation is less than or equal to +/- 5% for concentrations of less than 2 ng/ml and from +/- 0.2 to +/- 2% for higher concentrations. With this technique more sensitive, more specific, and twice as fast as similar ones, histamine content in 350-400 unknowns can be measured routinely in a working day. It has been used for more than 4 years and has proven to be a reliable and useful tool for the numerous research studies in which histamine is involved: immunology, allergy, pharmacology, dermatology, cancer, nutrition.

Basophils↗

PubMed1983

Evidence for a lymphokine enhancing arginase activity during allograft rejection.

The production of urea and ornithine is increased greatly in spleen cell cultures of an allograft recipient in the presence of donor cells (secondary MLC) in comparison to that of primary MLC (without previous allograft). This phenomenon appears after 24 hr of culture and reaches its maximum at 48 hr. The greatest increase in urea production is observed when the recipient spleen cells are collected at the time of allograft rejection. To obtain this extra production of urea, the stimulating cells in MLC should specifically be of the donor type or at least bear one homology with donor cells at the K or D locus. The increased production of urea and ornithine during MLC results from the action of a lymphokine released by recipient cells in the presence of donor cells. This factor acts upon cells present in bone marrow, spleen, and elicited peritoneal cells but is absent or is present in smaller quantities in thymus and lymph node cells. Target cells of this factor possess numerous macrophage features and could be immature cells of the macrophage line. The lymphokine responsible for this phenomenon is heat-stable, destroyed by trypsin, chymotrypsin, and neuraminidase, and has a m.w. around 32,000. It acts upon its target cells by increasing arginase activity, which results in the production of a large amount of ornithine, an important precursor of polyamine biosynthesis.

Amino Acids↗

PubMed1983

Skin allografts generate an enhanced production of histamine and histamine-producing cell-stimulating factor (HCSF) by spleen cells in response to T cell mitogens.

In response to T cell mitogens, spleen cells produce a large amount of histamine, whereas no or a slight increase is observed after B cell mitogen stimulation. This increased histamine production results from the effect of a factor having all the characteristics of HCSF (histamine-producing cell-stimulating factor) already described in secondary MLC supernatant. This factor is produced by Thy-1, 2, Lyt-1, 2-positive cells. Spleen cell cultures derived from skin-allografted mice during rejection produce more histamine in response to T cell mitogens than do spleen cells from normal or syngeneic grafted mice. Such a phenomenon is not observed in response to B cell mitogens. A striking association is found between enhanced histamine synthesis and skin allograft rejection. This phenomenon results from a) a five to 10-fold increase in HCSF production by allograft recipient spleen cells in response to T cell mitogens, and b) an increase in HCSF sensitivity of these spleen cells.

Animals↗