mast-cell-degranulating-peptide and Hypersensitivity

The solid phase synthesis of mast degranulating peptide (MCD peptide) raised the possibility of preparing analogs and examining the pharmacology and the proposed role of this peptide as a potential agent in allergy and inflammation. MCD peptide, a cationic 22-amino acid residue peptide with two disulfide bridges, causes mast cell degranulation and histamine release at low concentrations and has anti-inflammatory activity at higher concentrations. Because of these unique immunologic properties, MCD peptide may serve as a useful tool for studying secretory mechanisms of inflammatory cells such as mast cells, basophils, and leukocytes, leading to the design of compounds with therapeutic potential.

Topics: Animals; Cell Degranulation; Histamine Release; Humans; Hypersensitivity; Inflammation; Mast Cells; Peptides

Treatment with aqueous and aluminum hydroxide (Al[OH](3))-adsorbed purified honeybee (Apis mellifera) venom (HBV) preparations can reduce the incidence of side effects associated with venom immunotherapy.. The aim of the present study was to assess these purified HBV immunotherapy preparations in situ.. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize the distribution of HBV components. The preparations were administered on the back legs of naive Wistar rats. The rats were killed, and cryosectioned tissue sections were subjected to hematoxylin and eosin staining and MALDI-MSI analyses.. Low-density maps of tissue distribution of HBV peptides, such as secapin, mast cell degranulating peptide, and melittin (Api m 4) were detected in the tissue after administration of HBV immunotherapy preparations. In addition, release of biogenic amines, cytokines, and leukotrienes was observed, and the distribution of HBV allergens, such as Api m 1 and Api m 2, was shown. At the 24-hour time point, the major HBV allergen Api m 1 was still detected at the site of Al(OH)(3)-adsorbed HVB injection, whereas in the case of aqueous HBV preparation, all the allergens, as well as most of the biogenic amines, were cleared at the 24-hour time point.. The present study shows that the majority of low-molecular-weight HBV components are rapidly removed from the site of venom immunotherapy administration. Furthermore, Al(OH)(3)-adsorbed HBV preparation demonstrated a depot effect, prolonging the availability of bee venom allergens at the site of administration.

Topics: Allergens; Aluminum Hydroxide; Animals; Antigens, Plant; Bee Venoms; Bees; Biogenic Amines; Cryoultramicrotomy; Desensitization, Immunologic; Humans; Hyaluronoglucosaminidase; Hypersensitivity; Insect Proteins; Lasers; Melitten; Peptides; Phospholipases A; Rats; Rats, Wistar; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Water

Histamine may be released from rat peritoneal mast cells by compound 48/80 and peptide 401 in the presence and absence of extracellular calcium. The process is non-cytolytic and requires an intact cell metabolism. The release produced under both conditions is inhibited by disodium cromoglycate, theophylline, dibutyryl cyclic AMP and (at high concentrations) quercetin. The efficacy of the drugs in the absence of extracellular calcium cannot be explained in terms of their postulated effect on the calcium-gating mechanism operative in anaphylactic secretion. Alternative modes of action of the compounds are thus considered.

Topics: Animals; Bee Venoms; Bucladesine; Calcium; Cromolyn Sodium; Dose-Response Relationship, Drug; Female; Glycolysis; Histamine Antagonists; Histamine Release; Hypersensitivity; Male; p-Methoxy-N-methylphenethylamine; Peptides; Quercetin; Rats; Theophylline