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J A Raaijmakers

Publications and source records attributed to J A Raaijmakers.

14 recordsLinked to original sources
PubMed1992

In vivo priming of platelet-activating factor-induced eosinophil chemotaxis in allergic asthmatic individuals.

The cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 are important modulators of eosinophilia and eosinophil function. Eosinophil chemotaxis is known to be particularly sensitive for cytokine priming. In the present study, we compared chemotactic responses of eosinophils derived from peripheral blood of allergic asthmatics to responses of eosinophils from peripheral blood of healthy individuals. Eosinophils from allergic asthmatics exhibited a markedly increased sensitivity in their chemotactic response toward platelet-activating factor (PAF) compared with eosinophils from normal donors. In contrast, C5a-induced eosinophil chemotaxis between both groups was similar. This in vivo-primed phenotype could be mimicked in vitro, by preincubating eosinophils from peripheral blood of healthy individuals with picomolar concentrations of either GM-CSF, IL-3, or IL-5. The chemotactic response of eosinophils derived from the circulation of allergic asthmatic patients toward GM-CSF was significantly lower compared with the response of eosinophils of healthy individuals. Our data strongly suggest that release of cytokines may be an important in vivo priming mechanism for eosinophils in the circulation of allergic asthmatic patients. Such an in vivo priming can subsequently result in selective upregulation and downregulation of chemotactic responses toward various chemoattractants release in the lung tissue.

Asthma↗
PubMed1990

Beta-agonistic properties of tulobuterol, a new beta-sympathicomimetic drug, and its effects on pulmonary beta-adrenoceptor characteristics.

Radioligand binding studies have been developed to determine pharmacologic receptor characteristics in vitro. With this assay, not only the number and dissociation constant (KD) can be studied, but also the interaction of agonists with the receptor. We used this method to study a new beta 2-sympathicomimetic drug, tulobuterol (1-(0-chlorophenyl)-2-butylamino-ethanol hydrochloride). Two sets of experiments were performed. One set of experiments investigated the effects of tulobuterol and terbutaline in chronic administration, while the second set compared the beta-adrenoceptor-stimulating properties of tulobuterol with terbutaline and salbutamol. The effects of 10 days' administration of tulobuterol and terbutaline on beta-adrenergic characteristics in rats were assessed biochemically by means of radioligand binding studies on pulmonary membranes and functionally using isolated tracheal spirals. It was found that: (1) In vivo treatment with both drugs induced a reduction of the number of beta-adrenoceptors bound by 3H-dihydroalprenolol (3H-DHA); however, tulobuterol also induced an increased affinity for beta-adrenoceptor binding. (2) Tulobuterol induced a significant increase in the sensitization of tracheal smooth muscle, facilitating the relaxation of airway smooth muscle. The inhibition of 3H-DHA binding with the three drugs was best fit in a two-binding site model, showing high- and low-affinity binding sites. The high-affinity sites had similar KD values for terbutaline and tulobuterol (1.6 x 10(7) and 1.5 x 10(-7), respectively). The high-affinity sites for salbutamol had a higher KD value (9.4 x 10(-7), suggesting a lower affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1989

Inflammatory mediators and beta-adrenoceptor function.

In this study the, in vitro, influence of arachidonic acid metabolites on human beta-adrenoceptors was investigated. Incubation of normal human pulmonary membranes with PAF, LTB4 and LTC4 affected pulmonary beta-adrenoceptor properties, as was shown in radioligand binding studies. The same mediators were able to induce a decreased lymphocyte cAMP synthesis. It is concluded that beta-adrenoceptor deficiencies, that can be demonstrated in peripheral lung tissue of COLD patients, may result from pathological processes such as inflammation.

Arachidonic Acids↗
PubMed1989

Mast cell heterogeneity in human lung tissue.

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue. 2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells. 3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type. 4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell. 5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells. 6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine. 7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with anti-immunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4. 8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with anti-immunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.

Alcian Blue↗
PubMed1988

Mast cell subtypes from human lung tissue: their identification, separation, and functional characteristics.

The contribution of mast cell subtypes and their different mediators to the pathogenesis of chronic obstructive lung diseases (COLD) has not yet been established. In the present study, enzymatic digestion, centrifugal elutriation and Percoll gradient centrifugation were used to obtain two populations of mast cell subtypes from human lung tissue. Mast cell subtypes were challenged with anti-human IgE, propranolol, compound 48/80, or opsonized zymosan. Both subtypes were able to release histamine, but differed in the amount of the amine release. Only the formalin-sensitive and alcian blue-positive type (FS-AB) released histamine on challenge with opsonized zymosan. The same subtype was able to release leukotriene C4 (LTC4) after challenge with anti-human IgE. The other subtype, the formalin-insensitive and alcian blue-positive type (FI-AB), did not respond to opsonized zymosan and did not release LTC4 after challenge with anti-human IgE. Stimulation with propranolol or compound 48/80 did not release histamine from the FS-AB mast cells while the FI-AB mast cells released only about 10% of their histamine content upon challenge with these secretagogues.

Histamine Release↗
PubMed1988

The isolation of human lung mast cells by affinity chromatography.

A method of isolation has been developed to purify mast cells from human lung tissue. The purification steps are: (1) dispersion of human lung tissue in single-cell suspensions by enzymatic digestion, (2) partial purification by counterflow centrifugal elutriation, (3) Percoll gradient centrifugation, and (4) enrichment of the mast cells by affinity chromatography using anti-human IgE-Sepharose. Enzymatic dispersion yielded 0.6 +/- 0.2 x 10(6) mast cells per gram wet tissue with purities of 3.3 +/- 1.0% (mean +/- SEM n = 3). Elutriation and gradient centrifugation yielded 0.36 +/- 0.05 x 10(6) mast cells per gram lung tissue in fractions with purities of 30.8 +/- 10.7%. Enriched mast cell fractions were combined, and disposed of contaminating cells by affinity chromatography, thereby yielding 0.25 +/- 0.03 x 10(6) mast cells per gram lung tissue, and improving the purity to 75.3 +/- 8.3%. The purified mast cells were intact and vitality exceeded 95%. In this way from 1 g wet lung tissue 0.25 +/- 0.03 x 10(6) mast cells may be isolated with a mean recovery of 41.7 +/- 2.4% and a mean purity of 75.3 +/- 8.3%.

Cell Separation↗
PubMed1987

Quantitative determination of the lectin binding capacity of small intestinal brush-border membrane. An enzyme linked lectin sorbent assay (ELLSA).

A test to determine quantitatively the lectin binding sites in brush-border membranes has been developed. Highly purified bovine small intestinal brush-border membranes were prepared, and subsequently coated directly to the bottom of a microtiter plate. Soybean agglutinin conjugated with peroxidase was coupled to its binding sites in the brush-border membranes and the peroxidase activity was determined in a spectrophotometer. The number of soybean agglutinin binding sites in the brush-border membranes has been established by means of iterized computer fit analysis of the data, indicating values for maximal binding of 7.10(-7) M soybean agglutinin per mg of brush-border membrane protein and a dissociation constant of 1.5.10(-5) M.

Animals↗
PubMed1987

The isolation of inflammatory cells from normal human lung tissue.

An isolation procedure to obtain inflammatory cells from normal human lung tissue is described, consisting of four steps: an enzymatic digestion, centrifugal elutriation, gradient centrifugation and additional affinity chromatography (to obtain mast cells). The dispersed cell population consisted mainly of macrophages, pneumocytes type II, neutrophils and lymphocytes. Further separation by elutriation yielded pure macrophages and pure lymphocytes. The heterogeneous cell mixtures obtained at elutriation were separated by gradient centrifugation. This method yielded pure macrophages, lymphocytes and pneumocytes, and fractions containing eosinophils, mast cells or neutrophils were enriched considerably. Additional affinity chromatography with anti-human-IgE yielded a mast-cell fraction of 75%.

Cell Separation↗
PubMed1979

Effects of Haemophilus influenzae vaccination on the (para-)sympathic-cyclic nucleotide-histamine axis in rats.

To determine whether Haemophilus influenzae could be a factor in human atopy its effects were studied on the (para-)Sympathic Cyclic nucleotide-histamine axis in rats. Haemophilus influenzae vaccination induced changes in the cholinergic system compatible with higher cyclic GMP levels and enhanced histamine release. The authors suggest an involvement of the cholinergic system in Haemophilus influenzae vaccination effects.

Animals↗
PubMed1976

Loss of an adrenergic effect in swiss mice.

The effect of adrenaline on the amount of blood eosinophils (eosinophilia) which had been found in Swiss mice in earlier experiments was lost after a few generations. The hyperglycemic response to adrenaline had not been changed. Sensitivities to noradrenaline and adrenaline were as found earlier, but the sensitivity to isoprenaline was reduced. The reduction of beta-adrenergic responsiveness suggests variations in biochemical parameters of mice or the appearance of mice genetically less responsive to beta-adrenergic drugs in only a few generations.

Animals↗
PubMedDate not supplied

Comparison of vaccination of mice and rats with Haemophilus influenzae and Bordetella pertussis as models of atopy.

1. Rats and mice were vaccinated with Haemophilus influenzae in different vaccination schedules whereafter blood eosinophils were counted. In rats a single vaccination resulted in a dose-dependent effect on the blood eosinophil count in a pattern comparable with that after Bordetella pertussis vaccination. In a long-term vaccination schedule (five times a week for 5 weeks) rats developed a constant eosinophilia. In mice a single vaccination resulted in an eosinopenia of a consistent pattern which differed from the response after Bordetella pertussis vaccination; in a long-term vaccination schedule, eosinophilia was evoked for a period of about 13 days. 2. Thirty minutes after an adrenaline injection in vaccinated rats and mice with Haemophilus influenzae, hyperglycaemic and eosinophilic responses were measured. The eosinophilic response after adrenaline was inhibited in both species; the hyperglycaemic response in rats was unaltered, in mice the response was slightly but significantly (P less than 0.05) decreased. 3. The sensitivity to several drugs was tested in mice, 5 days after vaccination with Haemophilus influenzae or Bordetella pertussis. Haemophilus influenzae vaccination reduced the isoprenaline sensitivity and increased the noradrenaline sensitivity. Bordetella pertussis vaccination reduced the isoprenaline sensitivity while the sensitivity to histamine and adrenaline was raised. 4. The Haemophilus influenzae vaccinated experimental animal provides a model that is possibly more related to human atopy than the Bordetella pertussis vaccinated animal.

Animals↗