The mechanism of basophil histamine release in patients with periodontal disease.

Histamine release from washed peripheral blood basophils of thirty-three subjects with varying degrees of periodontal disease was studied. Dental plaque, serum and basophil leucocytes were collected from individual patients. There was no histamine release when autologous, washed sonicated plaque was added to leucocytes. However, the incubation of autologous plaque with serum at 37 degrees C for 30 min generated a factor which induced histamine release from basophils. This serum factor was stable to heat (56 degrees C, 30 min), eluted from a Sephadex G-100 column at a volume corresponding to a molecular weight of approximately 16,000 daltons and its action was inhibited by antibody to C5. This factor, therefore, is probably C5a. There was a variation in the degree of histamine release seen with the leucocytes of different donors. This variability was a property of the basophil rather than a function of the serum. Basophils from patients with gingival indices of 0.5 to 1.0 had significantly more histamine release than basophils from patients with gingival indices of less than 0.5 or greater than 1.5 (P less than 0.001). These experiments demonstrate that dental plaque activates serum to form C5a which in turn releases histamine from basophils. However, these experiments do not indicate a role for IgE in this reaction since the direct interaction of plaque with basophils did not cause histamine release. The release of mediators from mast cells could play an important role in the induction of the inflammatory response in periodontal disease.     

The mechanism of anaphylactic histamine release from rabbit leucocytes

Histamine release from rabbit leucocytes is temperature-dependent and requires the presence of calcium but not magnesium ions. It is inhibited by agents which reduce disulphide linkages, and by sulphydryl-blocking agents, but potentiated by certain dicarboxylic acids.     

Complement-mediated release of histamine from human basophils. III. Possible regulatory role of microtubules and microfilaments.

The release of histamine by normal human leukocytes (basophils) following in vitro challenge with activated complement (zymosan-treated serum) was previously reported. In this study, the effects of various pharmacologic agents on this release mechanism were compared with allergen-induced release of histamine. Colchicine and vinblastine antagonize the polymerization of tubulin to form microtubules, and both agents inhibited complement-and allergen-triggered release of histamine from basophils. Finally, treatment with cytochalasin B, a fungal product known to interfere with microfilament formatin, resulted in enhanced release of histamine from complement-treated basophils but no significant change in the percentage of histamine released from allergen-treated basophils. These findings suggest that microtubules and/or microfilaments are involved in complement-induced secretion of histamine by human basophils.     

Chronic idiopathic urticaria: Profiles of skin mast cell histamine release during active disease and remission

Chronic idiopathic urticaria (CIU) is characterized by the increased releasability of histamine by mast cells in normal-appearing skin. In active CIU, this abnormality is consistently present. To determine if this finding subsides when the disease goes into remission phase, we analyzed the histamine secretion in patients with CIU in remission (CIUR) compared with that of patients with CIU and in normal control (NC) subjects, with the skin-chamber technique. The profiles of histamine release in sites challenged with compound 48/80 were significantly different in the groups with CIU and CIUR. Furthermore, patients with CIUR did not differ from NC subjects in terms of histamine releasability under compound 48/80 stimulation (p greater than 0.1). These data suggest that the state of excessive skin mast cell sensitivity is a reversible and transient phenomenon in CIU disease.     

On the mechanism of histamine release induced by thapsigargin fromThapsia garganica L.

Thapsigargin (Tg) is a pure chemical compound isolated fromThapsia garganica with a molecular weight of 650. It releases histamine from isolated rat mast cells but not from isolated histamine-retaining mast cell granules. The rate of release is markedly influenced by pretreatment of mast cells with Tg prior to the addition of calcium. In agreement with the effect of the ionophore A23187 but in contrast to many other calcium-dependent histamine-releasing agents, cells preincubated with Tg respond to the secretory action of calcium whenever the ion is introduced. However, after dilution of Tg-pretreated cells histamine release induced by the addition of calcium became dependent on the time of its addition. The secretory reaction induced by Tg and calcium can be divided into a two-step reaction at 37°C. Pretreatment of mass cells with Tg renders the cells insensitive to the secretory action of compound 48/80 in the absence of calcium, and this effect could be partly counteracted if 1 mM of strontium was added together with compound 48/80. It is concluded that among various calcium- and energy-dependent histamine-releasing agents Tg most closely resembles the action of fluoride on isolated rat mast cells.     

14C-histamine release during vasodilatation induced by lumbar ventral root stimulation

Summary The vascularly isolated hindlimbs of dogs under chloralose anesthesia and neuromuscular blockade were perfused at constant flow with the animal's own arterial blood. Stimulation of the spinal ventral roots from L₅ to L₇ induced an antihistamine sensitive vasodilatation (VD) in the ipsilateral limb [Graham, Lioy: Histaminergic vasodilatation in the hindlimb of the dog. Pflügers Arch.342, 307–318 (1973)]. One hundred C of¹⁴C-histidine were injected into the limb perfusion line. Endogenously formed¹⁴C-histamine increased in the femoral venous blood from 59.2±17.0 to 190.3±41.9 cpm/ml of blood (P<0.005) during the VD induced by ventral root stimulation, while¹⁴C-histidine kept decreasing during the periods of observation. A significant increase of labeled histamine was also present upon ventral root stimulation after the VD had been drastically reduced or abolished by mepyramine maleate. It is concluded that the hindlimb VD under study is due to the nervously mediated release of histamine.     

Tryptase and histamine release during aspirin-induced respiratory reactions

The involvement of mast cells in the pathogenesis of aspirin (ASA)-induced respiratory reactions was investigated by measuring serum levels of tryptase, a neutral protease that is a specific marker of mast cell activation. ASA challenges were performed in 17 ASA-sensitive patients with asthma and rhinosinusitis, and tryptase and histamine levels were measured in their venous blood samples. In three subjects who experienced moderate to severe respiratory reactions extending to the skin and/or gastrointestinal tract, marked elevations of tryptase levels in postreaction serum samples (peak levels, 51.9 and 40.0 ng/ml) were discovered in two of these three subjects, and a small elevation of tryptase occurred in the serum of the third subject (3.1 ng/ml peak). Plasma histamine levels in postreaction samples were significantly elevated over baseline values in all three subjects (delta mean plasma histamine, 238 pg/ml versus 56 pg/ml for the remaining 14 subjects; p less than 0.04). In the remaining 14 subjects, who experienced similar respiratory reactions without extrapulmonary symptoms during aspirin challenge, changes in tryptase and histamine levels were not observed.     

Relevance of basophil histamine release changes during venom immunotherapy

We investigated the effect of rush and long-term venom immunotherapy on histamine release parameters in bee venom allergic patients. Ten patients received rush venom immunotherapy, and histamine release data were obtained immediately before and after treatment. 17 patients were assessed by histamine release 24 to 63 months after termination of long-term venom immunotherapy. A control group of 10 non-allergic subjects was included in this study. Histamine released from whole blood was determined in a sensitive radio-enzymatic assay using a single isotope technique. Bee venom phospholipase A-induced histamine release from whole blood proved to be a test procedure of high specificity and sensitivity. Eight of 10 untreated patients and no control subject showed significant antigen-induced histamine release. Results obtained from patients immediately after successful rush venom immunotherapy showed an important decrease (mean 45.9%) of total histamine content of basophil leukocytes in all patients. Antigen-induced maximum histamine release was found to be increased in one, decreased in two and unchanged in seven patients. In patients who received long-term immunotherapy cell sensitivity to phospholipase A was significantly lower than in a group of untreated patients (P less than or equal to 0.002). These results suggest that even years after discontinuation of immunotherapy, histamine release parameters reflect patients' protection from systemic sting reactions as assessed by sting challenges. Histamine depletion of basophils induced by rush immunotherapy may play an important role in patients' protection immediately after termination of the rush regimen.     

Forearm vasodilatation following release of venous congestion

1. The volume rate of forearm blood flow was measured with a mercury-in-rubber strain gauge, or with a water-filled plethysmograph, from 1 sec after termination of a 2-3 min period of venous congestion.2. When congesting pressure had been less than 18 mm Hg, average post-congestion flow (five subjects) was constant during approx. 10 sec and not significantly different from resting flow.3. When congesting pressure had been 30 mm Hg, average post-congestion flow (eight subjects) was 26% higher than resting, during 3-4 sec after release of congestion, but rose to 273% of resting during 4-6 sec after release of congestion.4. In other studies forearm vascular resistance had been found normal or increased during such venous congestion, and theoretical studies here indicated that passive mechanical factors could not account for the delayed occurrence of high post-congestion flow.5. It appears, therefore, that the forearm vascular bed dilates actively shortly after release of substantial venous congestion. It would seem more likely that a myogenic mechanism, rather than a metabolic one, is responsible.     

The mechanism of histamine release induced by the ionophore X537A from isolated rat mast cells. II. The relationship between increase of cell volume and histamine release

The ionophore X537A induced swelling of isolated rat mast cells parallel to histamine release. Both actions were depressed by extracellular calcium and BSA, temperatures below 37°C, NEM, PMSF, and TTX, and were enhanced by high potassium and pretreatment of the cells with ATP. DSCG, theophylline, and DFP enhanced the histamine release noted after 10 min of incubation without influencing the swelling action of X537A. The swelling action could not be separated from histamine release and it is suggested that it right be inherent in the mechanism of secretion induced by X537A. The present results further distinguish histamine release induced by the two ionophores X537A and A23187.     

On the mechanism of histamine release from sodium fluoride-activated mouse mast cells

We have found that sodium fluoride-induced histamine release from mouse mast cells occurs in two separate steps, activation in the presence of fluoride and absence of calcium, and secretion triggered by calcium. The amount of released histamine was dependent either on the time of cell exposure to fluoride or on the final fluoride concentration in the incubation medium.The secretory step depends on the concentration of extracellular calcium; it increased as the concentration of calcium was increased. However, a substantial part of the release was both calcium and energy independent. This part, probably cytotoxic, increased markedly at the highest concentration and with extended times of cell exposure to fluoride.Among other divalent cations tested only strontium could partly substitute calcium to trigger secretion. The activating action of fluoride slowly decayed with time and addition of calcium for up to 2 h caused histamine release. Both steps were dependent on temperature and pH and were inhibited by antimycin A, suggesting that the reaction was enzymatic.The action of fluoride on mouse mast cells closely resembles its action on rat mast cells; however, some differences were also observed.     

Sequential release of histamine and 5-hydroxytryptamine during pinnal anaphylaxis in the mouse.

Histamine and 5-HT have been demonstrated to be involved in pinnal anaphylaxis in mice. Each predominates at different stages during the 30-min development of the reaction. The main mediator of the early stage of the reaction (0-10 min) is histamine, that of the middle stage (10-20 min) is 5-HT, and that of the final 20- to 30-min stage is, again, histamine. The source and mechanism of release of the 5-HT and the late histamine are, as yet, unknown but under investigation.     

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.     

Endotoxins release histamine by complement activation and potentiate bacteria-induced histamine release

The histamine-releasing capability of bacterial lipopolysaccharides (LPS) was examined in human leukocyte suspensions. LPS alone did not release histamine, but it was found to enhance the histamine release caused by bacteria in basophils from persons sensitized to these bacteria. In the presence of serum, LPS was able to release histamine through complement activation. It is speculated that endotoxins reinforce release of histamine caused by bacteria in persons sensitized to these microorganisms, and a direct mediator release via complement activation might play a role in septic conditions.