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Biomedical subjects

C Burtin

Publications and source records attributed to C Burtin.

At least 37 records · Page 2Linked to original sources

Evidence for serotonin (5HT) binding sites on murine lymphocytes.

The binding of 3H-labeled serotonin (or 5-hydroxytryptamine: 5HT) to mouse lymphocytes was investigated. It was shown to be highly specific, time-dependent, saturable and partly reversible. Saturation analysis demonstrated a Kd of 198 nM and B max of 3.53 nM. We studied receptor specificity by using different types of serotonin antagonists, and numerous other substances. Serotonin was found to be the most effective drug among those tested in inhibiting the binding of 3H-5HT, having an IC50 of 194 nM. The fact that 5HTP, a 5HT precursor, had no inhibitory capacity indicated the high specificity of these 5HT binding sites. Dopamine was somewhat able to competitively inhibit 5HT fixation (IC50 = 27,000 nM), whereas norepinephrine and histamine had no effect. Lastly, we investigated the cellular specificity of this binding, and observed that nonmacrophage peritoneal cells extensively bound serotonin under the same conditions as spleen cells. This is the first direct demonstration of 5-hydroxytryptamine receptors on mouse lymphocytes. The presence of these binding sites can contribute to the understanding of the suppressive effect of 5HT on mouse immunoreactivity.

Animals↗

Renal anaphylaxis. I. Antigen-initiated responses from isolated perfused rat kidney.

Isolated perfused rat kidneys were passively sensitized by addition of either mouse ascitic fluid containing monoclonal IgE against dinitrophenol (DNP) or DNP-specific purified IgE. After washing the organ, defined doses of DNP-bovine serum albumin were given as bolus injection via the kidney artery. Antigen challenge of IgE-sensitized kidneys resulted in a dose-dependent increase of perfusion pressure starting with 5 micrograms antigen (2.46 +/- 0.2 mm Hg) and reaching a maximum at dose higher than 100 micrograms (10.3 +/- 1.6 mm Hg) (N = 4, means +/- 1 SD). A decrease of glomerular filtration rate was also observed which reached a plateau at 100 micrograms antigen (-68.5 +/- 2.9%) (N = 4). Regardless of the dose of antigen used, the urinary protein excretion markedly increased for the first five minutes following antigen injection and returned to basal values after 10 minutes. The total amounts of histamine, PGE2 and paf-acether (platelet-activating factor) released upon antigen challenge (1 mg) for 15 minutes reached maximal values of 405 +/- 21.1 ng, 286 +/- 19.4 pg and 12.3 +/- 3.2 ng (N = 5), respectively. None of these hemodynamic and biochemical effects were observed using IgG1 monoclonal antibodies or when the ascitic fluid containing monoclonal IgE used to sensitize the organ was heated at 56 degrees C for two hours. Thus, we have described a pure IgE-dependent rat kidney anaphylaxis. Antigen challenge markedly altered renal parameters and triggered the release of various mediators from the organ, suggesting that type I-hypersensitivity reactions may play a role in renal pathophysiology.

Anaphylaxis↗

Role of mast cells in the pathogenesis of hypersensitivity pneumonitis.

To examine the possibility that mast cells have a central role in the pathogenesis of hypersensitivity pneumonitis, 20 patients with this disease were studied with the aim of seeking evidence for mast cell degranulation. The number of mast cells recovered by bronchoalveolar lavage from patients with hypersensitivity pneumonitis was more than 1,000 times greater than those recovered from normal individuals. Furthermore, discontinuation of antigen exposure resulted in an increase in the number of mast cells observed, consistent with the possibility that antigen exposure had induced mast cell degranulation. Cessation of antigen exposure also resulted in a rapid decrease in the number of neutrophils and eosinophils recovered by lavage, followed by an increase in the number of T8+ T lymphocytes present. In each case the time course of the changes was consistent with the possibility that mast cell degranulation had been important in regulating the number of the immune and inflammatory cells present in the lung. Histamine was present in lavage fluid supernatant from patients with hypersensitivity pneumonitis. The amount of histamine present was, however, closely correlated with the number of mast cells present and not with the interval since last antigen exposure. Delay in separating cells from lavage fluid supernatant resulted in an increase in histamine content. These results suggest that the free histamine in lavage fluid resulted from the degranulation of mast cells induced by the lavage procedure as histamine released in vivo has a short half life. We suggest that hypersensitivity pneumonitis results from a "late phase reaction" initiated by antigen induced mast cell degranulation.

Alveolitis, Extrinsic Allergic↗

Acute hemodynamic effects of an antitumoral agent: elliptinium. Involvement of histamine release.

This work reports a study of cardiovascular effects of elliptinium, a recently-acquired antitumoral agent, acutely administered i.v. in the dog. Its hemodynamic effects (10 parameters) are detailed, and their mechanism of action is investigated by antagonist administration and determination of blood and plasma histamine levels. Elliptinium induces vasodilation and tachycardia. The former is mainly due to histamine release, and a brief and slight release of prostaglandins; the latter is due to a reflex to hypotension and release of catecholamines. These results agree with others using various compounds of the ellipticine family and anthracycline antitumoral agents. They suggest treatment to prevent anaphylactoid side effects observed with this drug in man and they raise the question of the usefulness, in antitumoral agent, of histamine releasing properties.

Alkaloids↗

Decreased skin response to intradermal histamine in cancer patients.

The skin response to intradermal injections of serial dilutions of histamine was studied in 68 cancer patients and 29 noncancer, nonallergic subjects. In cancer patients with primary tumor with or without metastasis, incidence and size of wheals and flare were markedly depressed by comparison with control subjects. Pseudopods were rare, and itching was absent. Similar results were observed in patients in which excisions of the primary tumor dated from less than 5 weeks. In contrast, when excision dated from greater than 2 months, skin tests returned to almost normal values. Intermediate values were obtained in patients with metastases alone. This decrease in skin response to histamine was not due to a peripheral neuropathy in cancer patients, since results of electrophysiologic studies were not different in cancer and noncancer patients. The presence of a tumor mimics the effects of general administration of histamine H1 antagonists on the skin response to histamine.

Adult↗

Tissue histamine levels in male and female mast cell deficient mice (W/Wv) and in their littermates (Wv/+, W/+ and +/+).

Histamine levels have been determined in nine tissues of four kinds (W/Wv, Wv/+, W/+, +/+) of WBB6F1 male and female mice, and mast cells have been counted in the skin and the fundus of W/Wv and +/+ mice. By comparison with +/+ mice (1) the association of the two alleles Wv and W induced a drastic decrease in tissues histamine levels and in mast cell number. (2) The allele Wv alone induced a marked decrease in tissue histamine levels but less important than the two alleles W and Wv. (3) In contrast, the allele W alone induced at least in some tissues, an increase in tissue histamine levels. In W/+, Wv/+ and +/+ fertile mice, tissue histamine levels were higher in females than in males. In contrast, in W/Wv mice which are sterile, no difference between males and females was observed.

Alleles↗

In vivo and in vitro anti-tumour activity of dimaprit.

Dimaprit, a histamine H2-receptor agonist, injected daily i.p. to fibrosarcoma-bearing mice, induced a decrease in tumour growth and an increase in survival. Dimaprit, added to tumour cell cultures (10(-4) M), inhibited the incorporation of 3H-thymidine while embryonic cell cultures were unaffected. This particular anti-tumour activity is probably H2-independent as histamine and impromidine have no effect on tumour cell cultures.

Animals↗

Inverse correlation between tumor incidence and tissue histamine levels in W/WV, WV/+, and +/+ mice.

The influence of mast cells on tumor incidence and growth rate was studied in 2 grafted tumor models (fibrosarcoma MC-B6-1 and the Lewis lung carcinoma 3LL). Three kinds of WBB6F1 mice (a cross between WB/ReJ-W/+ and C57BL/6J-WV/+ mice) were used: W/WV (deeply mast cell depleted), WV/+ (partially mast cell depleted), and +/+ (normal mast cell number). The presumed resistance of F1 hybrids to tumor cells of parental origin was observed in 12 of 13 +/+ mice, but only in 11 of 22 WV/+ mice and in none of 39 W/WV mice. Tumor incidence and metastasis incidence were inversely correlated with tissue histamine levels and mast cell number. Growth rates of tumors were similar in W/WV and WV/+ mice, but the tumor growth rate was much slower in the only +/+ mouse in which the tumor grew. These results confirm the protective role of mast cells against tumors.

Animals↗

Tissue histamine levels and mast cell numbers in tumour-bearing mice.

In C57BL/6 mice bearing the 3LL carcinoma and in C3H mice bearing the McC3 -1 fibrosarcoma (18th passage), the increase in skin histamine levels was correlated with the increase in mast cell number. The number of cells able to incorporate tritiated thymidine was proportional to the mast cell number. These results strengthen the notion that, in tumour-bearing rodents, the increase in tissue histamine is an active phenomenon.

Animals↗

Histamine and serotonin suppression of lymphocyte response to phytohemagglutinin and allogeneic cells.

Histamine added to murine spleen cells suppressed in vitro proliferation of lymphocytes induced by PHA or allogeneic spleen cells. Another vasoactive amine, serotonin (5-hydroxytryptamine), exerted a similar inhibitory activity on PHA- or allogeneic cell-induced lymphocyte proliferation. Anti-H2 histamine antagonists, cimetidine, metiamide, and ranitidine, blocked the histamine and serotonin suppressive effect. Cyproheptadine, an anti-H1 histamine and anti-serotonin antagonist, and methysergide, an anti-serotonin antagonist, also blocked histamine and serotonin inhibitory activities. These data suggest the presence, on lymphocytes, of receptors for serotonin which might be related to histamine receptors.

Animals↗

Release of platelet-activating factor, slow-reacting substance, and vasoactive amines from isolated rat kidneys.

The present work brings the first evidence for the simultaneous release of Paf-acether (platelet-activating factor), slow-reacting substance (SRS), histamine, and serotonin from isolated rat kidneys stimulated with ionophore A 23187. However, with compound 48/80 we detected only SRS, histamine, and serotonin. Upon addition of antigen, kidneys from sensitized rats released Paf-acether and SRS of anaphylaxis. Paf-acether released in the perfusate was identified by its ability to aggregate aspirin-treated washed rabbit platelets in the presence of an ADP scavenger complex. It was also characterized by its inactivation by phospholipase A2, and it was eluted from high pressure liquid chromatography (HPLC) after 16 to 18 min, a retention identical to that of synthetic Paf-acether, that is, between sphingomyelin and lysophosphatidylcholine. The biological activity of SRS was detected after several purification steps including Amberlite XAD-2 and reverse phase HPLC (RP-HPLC). Kidney SRS exhibited a typical spasmogenic activity in isolated guinea-pig ileum preparation that was reversed by FPL 55712. When kidneys were incubated with [3H]arachidonic acid, radioactivity and biological activity comigrated in RP-HPLC with leukotrienes C and D. These results indicate that the kidney is capable of actively released inflammatory mediators.

Animals↗

Noninvolvement of histamine and prostaglandins in the dermatosis of magnesium-deficient hairless rats.

Hairless rats receiving a deprived Mg2+ diet developed long-lasting inflammatory dermatosis which was not influenced by treatments with mepyramine, cimetidine, aspirin or indomethacin. Dermatosis did not appear in deprived rats treated with intraperitoneal injections of Mg2+, or with dexamethasone. Histamine and prostaglandins did not seem to be involved in this dermatosis. The possible role of leucotrienes is discussed.

Animals↗

Selective increased tissue histamine levels in tumour-bearing rodents.

Histamine levels increased in the fundus of mice bearing a primary 3-methylcholanthrene-induced fibrosarcoma, and in the ventral skin, skeletal muscle and rumen of rats bearing a D.M.B.A. induced mammary adenocarcinoma; they did not increase in the tissues of mice bearing a McC3-1 fibrosarcoma (38th passage) or a Lewis lung carcinoma before the appearance of metastasis, but an increase in histamine levels was observed in dorsal skin, ventral skin and fundus, after the appearance of metastasis.

Animals↗

Decreased blood histamine levels in patients with solid malignant tumours.

In a one-year follow-up study, 444 blood histamine determinations were performed in 163 patients with solid malignant tumours. Compared with normal subjects, blood histamine levels were significantly lower in patients with unresected primary tumours (30.7 +/- 19.9 ng ml-1), metastases (34.1 +/- 17.1 ng ml-1), or both (24.5 +/- 12.8 ng ml-1). By contrast, after successful tumour resection, histamine blood levels were nearly normal (52.1 +/- 18.4 ng ml-1, versus 59.6 +/- 22.6 in control patients). Stability of the histamine blood levels was associated with stability of the disease. A progressive decrease in histamine blood levels preceded clinical relapse or detection of metastasis. In patients with consecutive histamine blood levels which were less than 15 ng ml-1, survival did not exceed 2 months. In patients with gastrointestinal tumours, blood histamine levels provided information additional to that derived from serum CEA determination. In patients with non-gastrointestinal tumours, the blood histamine level may be of more value than CEA as a marker of disease progression.

Adult↗

Tissue histamine levels in male and female normal and nude mice.

In comparison with those in normal (+/+) mice, tissue histamine levels were lower in athymic (nu/nu) female mice and higher in athymic male mice. The sexual difference was less marked or absent in nu/nu mice. These results show (a) that endocrine factors are involved in the distribution of tissue histamine, and (b) that the thymus cannot be considered as the main source of tissue histamine in pathogen-free mice.

Animals↗

Decrease in tumour growth by injections of histamine or serotonin in fibrosarcoma-bearing mice: influence of H1 and H2 histamine receptors.

C3H and C57 BL/6 mice carrying methylcholanthrene-induced fibrosarcomas were injected i.p. daily with histamine, metiamide (anti-histamine type-2 receptor), histamine + metiamide, mepyramine (anti-histamine type-1 receptor), serotonin and methysergide (anti-serotonin). Inhibition of tumour growth and lengthened survival were observed with histamine and histamine + metiamide. The best results (both on tumour growth and survival) were obtained with serotonin. Survival was increased by metiamide and decreased by mepyramine and methysergide. In histamine-treated and in serotonin-treated mice, histological studies of the tumours showed large and numerous foci of haemorrhagic necrosis. Stimulation of histamine type-1 or serotonin receptors and inhibition of histamine type-2 receptors play a beneficial role in the host's defence against tumours.

Animals↗

Histamine-releasing properties of hydroxy-9-methyl-2-ellipticinium acetate.

Previous work on Hydroxy-9-methyl-2-ellipticinium acetate indicated a bronchoconstrictor activity which could be partially offset by antagonists of the H1 histamine receptors, and the absence of any direct effect on smooth muscle. OH-9-CH3-2-E at concentrations of 10 micrograms/ml and 500 micrograms/ml produced a moderate and a variable release of histamine when placed in contract with whole human blood and lung fragments, respectively. In addition, at a dose of 3 mg/kg in the guinea pig, pulmonary airway resistance was raised and the blood histamine level lowered. A significant correlation was found between these two effects. These results demonstrate that OH-9-CH3-2-E possesses a histamine-releasing potency which is partly responsible for its bronchial effects, implying that precautions may have to be taken when it is used as a therapeutic agent in sensitive subjects. However, the moderate intensity of this potency has not so far precluded therapeutic use of the preparation.

Airway Resistance↗