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Biomedical subjects

W Boucher

Publications and source records attributed to W Boucher.

48 records · Page 3Linked to original sources
PubMedDate not supplied

Rapid degradation of neurotensin by stimulated rat mast cells.

A RIA towards neurotensin (NT) using C-terminal- and N-terminal-specific antisera was used to study degradation of this tridecapeptide by isolated rat mast cells. Incubation of NT (10 microM) with peritoneal or pleural mast cells resulted in a rapid loss of NT immunoreactivity (iNT), as measured by C-terminal-directed antiserum, with little effect on N-terminal iNT. The rate of the reaction was faster with pleural cells (T1/2, 30 s) than with peritoneal cells (T1/2, 180 s) and was greater than 10-fold slower in the presence of metabolic poisons. The enzyme(s) involved is most likely released from the cells during secretion, as NT was degraded by media conditioned by compound 48/80-stimulated mast cells 40-60 times faster than by media from unstimulated cells. This degradation by conditioned media was concentration dependent, pH dependent, and temperature sensitive. HPLC analyses indicated a near stoichiometric conversion of NT to NT(1-12) (66%) and NT(1-11) (34%) after incubation for 10-30 s with conditioned media. By 30 min only NT(1-11) and NT(1-10) were present. Phenanthroline (1 mM), an inhibitor of carboxypeptidase, prevented the loss of C-terminal iNT and the generation of NT(1-12) and NT(1-11). While NT(1-12) was effective in releasing histamine from mast cells in vitro and increasing vascular permeability in vivo, NT(1-11) was not. These results suggest that carboxypeptidase-like enzyme(s) could modulate the level and form of NT-related peptides in various states involving activation of mast cells.

Amino Acid Sequence↗
PubMedDate not supplied

Stimulated rat mast cells generate histamine-releasing peptide from albumin.

Media conditioned by compound 48/80-stimulated rat mast cells generated immunoreactive histamine-releasing peptide (HRP) when incubated at physiological pH with bovine serum albumin and the carboxypeptidase inhibitor, O-phenanthroline. The generation of immunoreactive HRP (IR-HRP) was time (after 3 h the concentration of IR-HRP was 20 nM), temperature, and pH dependent and was prevented by omitting albumin, by using media conditioned by nonstimulated mast cells, or by pretreatment of mast cells with disodium cromoglycate, an inhibitor of mast cell secretion. The amount of IR-HRP generated increased linearly with the number of mast cells stimulated and varied directly with the concentration of conditioned media. After removal of the media from stimulated mast cells, the remaining cell pellet retained its ability to generate IR-HRP for up to 8 h. Stimulation of mast cells by either neurotensin or substance P, or of sensitized cells by anti-IgE serum, also produced conditioned media that generated IR-HRP. The amount of IR-HRP formed by various conditioned media or by stimulated cell pellets was dependent upon the concentration of O-phenanthroline used. Including the chymase inhibitor, chymostatin, prevented the formation of IR-HRP in a dose-dependent manner. HPLC analysis showed four peaks of IR-HRP. The major one coeluted with synthetic HRP. These results indicate that the peptide, HRP, can be generated by stimulated mast cells incubated in the presence of albumin. They suggest that a chymase-like enzyme secreted by the mast cell is able to cleave albumin to yield HRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMedDate not supplied

Inhibitory effect of retinoic acid on proliferation, maturation and tryptase level in human leukemic mast cells (HMC-1).

Mast cells play important role in allergic inflammation by releasing histamine, tryptase and several inflammatory cytokines. Human leukemic mast cells (HMC-1) have been used to study mast cell mediator and their role in inflammatory mechanisms. HMC-1 contain and release several inflammatory mediators, of which the proteolytic enzyme tryptase is most characteristic. Retinoids, including retinoic acid, are naturally occurring and synthetic derivatives of vitamin A. All-trans-retinoic (ATRA) acid had been previously reported to inhibit cell proliferation, differentiation and apoptosis. In the present study, we investigated the effect of ATRA on the proliferation and secretion of tryptase in HMC-1. HMC-1 were treated with ATRA at 10(-4M), 10(-5M) or 10(-6M) for 3, 4 or 5 days in culture. Control HMC-1 were treated with equal amount of culture medium only. ATRA decreased the number of HMC-1 as compared to the control group. The same treatment for 3, 4 or 5 days also decreased intracellular tryptase levels. These results indicate that ATRA significantly inhibits both proliferation and growth as shown by the decreased intracellular tryptase levels in HMC-1. ATRA may be a useful agent in the treatment of mast cell proliferative disorders.

Cell Differentiation↗
PubMedDate not supplied

Cytokines in stress.

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Animals↗
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Theophylline as "add-on" therapy in patients with delayed pressure urticaria: a prospective self-controlled study.

Delayed pressure urticaria (DPU) is a skin condition that involves the gradual development of wheals and edema at sites of physical pressure. Its pathogenesis is not clear and histamine-1 receptor (H-1R) antagonists provide only partial relief. In this prospective, clinical study, we investigated the effect of theophylline, which has a long history of benefit in allergic asthma, added to cetirizine in patients with DPU. Twenty three patients received during period 1 cetirizine (10 mg po QD) and theophylline (200 mg po BID) for 6 months, followed by period 2 of 1 month washout with only rescue medication as needed, and then by period 3 with cetirizine (10 mg QD plus placebo (BID) for 5 more months. The addition of theophylline resulted in statistically significant improvement over cetirizine alone by 2 months and continued for the duration of treatment. Treatment of cultured human mast cells with theophylline (10 microM) did not inhibit allergic histamine release, but the in vivo beneficial effect of theophylline may require significant pretreatment period to manifest itself, or may involve inhibition of other mast cell dependent mediators. A double-blind study, accompanied by serum histamine and tryptase levels, should be in order.

Adult↗
PubMedDate not supplied

Progesterone inhibits mast cell secretion.

Mast cells are involved in allergic reactions, where they secrete numerous vasoactive, inflammatory and nociceptive mediators in response to immunoglobulin E (IgE) and antigen. However, they have also been implicated in inflammatory conditions, such as painful bladder syndrome/interstitial cystitis (PBS/IC), irritable bowel syndrome (IBS) and migraines, all of which occur more often in women and are exacerbated during ovulation, but are suppressed during pregnancy. Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it. Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.

Animals↗