Tadao Okazaki

Regulatory role of prostaglandin E in allergic histamine release with observations on the responsiveness of basophil leukocytes and the effect of acetylsalicylic acid.

Abstract This study examined the relationship between prostaglandin E (PGE) production and antigen-induced histamine release by leukocytes of asthmatic patients. The maximum amount of antigen-induced histamine release from leukocytes of different donors did not correlate with serum ragweed-specific IgE levels and correlated inversely with the basal PGE release from cultured leukocytes. The relationship betwen maximum histamine release and serum ragweed-specific IgE levels appeared to be influenced by the degree of PGE release. Patients with lower histamine release relative to ragweed-specific IgE levels had elevated PGE release. Based on these findings it can be hypothesized that spontaneously produced PGE might be a determinant of the responsiveness of basophil leukocytes to immunologic stimulation. This hypothesis was supported by demonstration of a positive correlation between the degree of inhibition of total basal PGE production in leukocyte suspensions during a short period of incubation and the degree of enhancement of antigen-induced histamine release by acetylsalicylic acid (ASA). The results indicate that, although the presence of IgE antibody in the blood may be the prerequisite for allergic histamine release from human leukocytes, endogenous PGE may be an important regulator of the release reaction. The results also suggest that idiosyncratic reactions to ASA and other nonsteroidal anti-inflammatory drugs observed in the allergic population may be at least partly due to impairment of the regulator function of endogenous PGE in the IgE-mediated histamine release reaction.

Inhibition of antigen-induced histamine release by ouabain

The effect of ouabain, a specific sodium-potassium dependent adenosine triphosphatase (Na+-K+-ATPase) inhibitor, on antigen-induced histamine release was studied using guinea pig lung fragments sensitized in vitro with rabbit antibodies against bovine serum albumin. Histamine was assayed spectrofluorometrically. When sensitized tissue had been preincubated with ouabain (less than or equal to 1.0 x 10(-4) M) for 10 min prior to antigenic challenge, release of histamine was significantly inhibited (maximum 54%, p less than 0.001, N=9, paired t test). The most significant inhibition was obtained near the optimal concentration of antigen. The inhibition was dependent on the length of preincubation (less than or equal to 20 min), and was partially reversible upon washing the tissue removing the ouabain. Ouabain did not seem to prolong the duration of the histamine release process. Increase in potassium ion (less than or equal to 1.1 x 10(-2)M) inhibited the histamine release and had additive effects to ouabain action. Dibutyryl cyclic AMP (less than or equal to 5 x 10(-3) M), which could enhance the release, strongly antagonized the inhibition. Glucose removal from the medium did not abolish the ouabain effect. The results seem to indicate that immunologic release of histamine is under the influence of the membrane Na+-K+-ATPase activity.

Prostglandin E in the secretions of allergic rhinitis

Prostaglandin (PG) was extracted from nasal secretions of individuals with hay fever and from nasal washings of normal subjects. The extract was chromatographed in a silicic acid column and the purified PGE fraction was converted to PGB by alkaline dehydration. The PGB was then measured by a competitive radioimmunoassay with tritiated PGB1 and anti-PGB1 antibody, employing the double antibody technique. PGE was detected in the secretions of 6 of 12 hay fever patients and in the pooled normal nasal washings.

Prostaglandins and asthma: The use of blood components for metabolic studies

Experiments were carried out to study a possible role of prostaglandins (PGs) in the pathogenesis of human bronchial asthma. Leukocyte, plasma, and serum of ambulatory asthmatic as well as nonasthmatic individuals were used. PGF was measured by competitive radioimmunoassay with anti-PGF2alpha antibody. It was found that PGF was spontaneously released from the leukocytes of both asthmatic and nonasthmatic individuals. The PGF release as studied with the cells of asthmatic individuals was enhanced by the additions of arachidonic acid and/or dibutyryl cyclic AMP. Antigenic challenge of sensitive cells failed to show any general effect on the amount of PGF released. The amount of spontaneously released PGF had no correlation with the amount of maximal antigenic histamine release. Preincubation of the cells with arachidonic acid had no effect on subsequent antigenic histamine release. Plasma PGF levels in nonasthmatic and in asthmatic individuals were not significantly different and both were considerably lower than the serum levels. The mean serum PGF level in the asthmatic group was higher than in the nonasthmatic, indicating probably a greater release of PGF from blood cells.

Prostaglandin E and mitogenic stimulation of human lymphocytes in serum-free medium.

Sera used in cell cultures contain significant ammounts of prostaglandins (PGs). In order to avoid any effects of contaminating PGs, the present study employed a serum-free culture medium and confirmed the inhibitory effect of prostaglandin E (PGE) on the human lymphocyte activation which had been observed previously employing a serum-containing medium. PGE1 displayed a significantly stronger inhibitory effect on the cells than previously shown. Furthermore, reported enhancement of PGE synthesis by mitogen-activated lymphocytes could not be reproduced.

Glycogenolysis and control of anaphylactic histamine release by cyclic adenosine monophosphate-related agents: I. Role of glycogen and glucose☆☆☆

The relationship of glycogen and glucose to anaphylactic histamine release from chopped sensitized guinea pig lung in vitro was studied. A parallelism was observed between the total amount of glycogen in the sensitized lung and the total amount of histamine released from the lung by antigen-antibody reactions. Removal of glucose from the medium for tissue suspension resulted in reduction in histamine release. Depletion of glycogen and/or glucose from the system was associated with (1) abolition of the inhibition of histamine release by isoproterenol and high concentrations of dibutyryl cyclic adenosine monophosphate (AMP) and (2) increase in the rate of enhancement of histamine release by lower concentrations of dibutyryl cyclic AMP. The results indicate that (1) glycogen may be one of the ultimate energy sources for anaphylactic histamine release, and (2) the presence of adequate amounts of glycogen and/or glucose in the sensitized tissue is necessary for the normal beta adrenergic effects on the histamine release in vitro from sensitized lung fragments.

Histamine release from human leukocytes: Modulation by cadmium ion

The effect of cadmium on histamine release was studied in relation to the role of calcium. The antigenic histamine release from peripheral leukocytes of ragweed-sensitive patients was inhibitied in the presence of cadmium (greater than 10(-5) M). Spontaneous histamine release was not affected by cadmium except for an enhancement observed in high concentrations (greater than or equal to 10(-3)M). Cadmium did not seem to affect the first stage of histamine release but to act mainly on the calcium-dependent second stage. Increasing the level of calcium in the medium could antagonize the inhibitory effect of cadmium. The effect of cadmium could be totally abolished by deuterium oxide and partially by dibutyryl cyclic adenosine monophosphate (AMP) in certain concentrations. These results would indicate that: (1) cadmium acts as an antagonist of calcium and can be used for the study of the role of calcium in histamine release, (2) the action of calcium in the histamine release reaction seems to be related to the microtubular system, (3) cyclic AMP may potentiate histamine release when the action of calcium is inhibited.

Glycogenolysis and control of anaphylactic histamine release by cyclic adenosine monophosphate-related agents: II. Modification of histamine release by glycogenolytic metabolites

D-glucose-6-phosphate (less than or equal to 5 x 10(-3) M), pyruvate, lactate (less than or equal to 1 X 10(-2) M), and dibutyryl cyclic AMP (less than 5 X 10(-3) M) were capable of inhibiting anapylactic histamine release in vitro from chopped guinea pig lung. In lower concentrations, pyruvic acid and lactate, as well as dibutyryl cyclic AMP, enhanced the release. Significant synergism was observed betweenpyruvate (5 X 10(-3) M) and isoproterenol (1 X 10(-8) M) in the inhibition of histamine release. The inhibitory actions of isoproterenol, glucose-6-phosphate, and pyruvate were influenced by calcium ion concentration. However, beta blockade, which diminished the isoproterenol effect, was without efect on pyruvate (1 X 10(-2) M) to the release system. Glucose-6-phosphate and isoproterenol did not have this effect. The results, together with a prevouus study, suggest that glycogenolysis may possess a role in the anaphylactic istamine release in vitro from sensitized lung fragments...

The effect of Tris-buffered media and Tyrode physiologic saline solution on the antigenic release of histamine from human leukocytes

Allergic histamine release from leukocytes was compared in three different media: Tyrode physiologic saline solution, Tris-buffered saline containing human albumin, calcium, and magnesium (Tris-ACM), and Tris-ACM with homologous serum. In a selected group of low histamine releasers, the maximal amount of antigenic histamine release was significantly higher in Tyrode solution as compared to Tris-ACM buffer. When homologous serum was added to Tris-acm, an enhancement of histamine release greater than with Tyrode solution was obtained. These results suggest that Tris-ACM may not be the optimal buffer for leukocyte histamine release experiments. Since Tyrode solution contains no serum proteins that bind slow-reacting substance of anaphylaxis or prostaglandins, the use of this medium may be advantageous for the study of the release of the chemical mediators from human leukocytes.

Plasma Prostaglandin Concentrations in Allergic Bronchial Asthma

Prostaglandin (PG) E plasma levels, measured by radioimmunoassay using anti-PGB1 antibody, were higher in asthmatic patients than in normal subjects. PGF levels measured with anti-PGF2alpha antibody, were not significantly different between normals and asthmatics. Plasma PGE/F ratios were elevated in the asthmatic patients. The results fail to support the hypothesis of decreased PGE or increased PGF production as an etiological factor in asthma.