PMID- 11082109
OWN - NLM
STAT- MEDLINE
DCOM- 20010202
LR  - 20181130
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 131
IP  - 6
DP  - 2000 Nov
TI  - Chondroitin sulphate inhibits connective tissue mast cells.
PG  - 1039-49
AB  - 1. Mast cells derive from the bone marrow and are responsible for the development 
      of allergic and possibly inflammatory reactions. Mast cells are stimulated by 
      immunoglobulin E (IgE) and specific antigen, but also by a number of 
      neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to 
      secrete numerous pro-inflammatory molecules that include histamine, cytokines and 
      proteolytic enzymes. 2. Chondroitin sulphate, a major constituent of connective 
      tissues and of mast cell secretory granules, had a dose-dependent inhibitory 
      effect on rat peritoneal mast cell release of histamine induced by the mast cell 
      secretagogue compound 48/80 (48/80). This inhibition was stronger than that of 
      the clinically available mast cell 'stabilizer' disodium cromoglycate (cromolyn). 
      Inhibition by chondroitin sulphate increased with the length of preincubation and 
      persisted after the drug was washed off, while the effect of cromolyn was limited 
      by rapid tachyphylaxis. 3. Immunologic stimulation of histamine secretion from 
      rat connective tissue mast cells (CTMC) was also inhibited, but this effect was 
      weaker in umbilical cord-derived human mast cells and was absent in rat 
      basophilic leukemia (RBL) cells which are considered homologous to mucosal mast 
      cells (MMC). Oligo- and monosaccharides were not as effective as the 
      polysaccharides. 4. Inhibition, documented by light and electron microscopy, 
      involved a decrease of intracellular calcium ion levels shown by confocal 
      microscopy and image analysis. Autoradiography at the ultrastructural level 
      showed that chondroitin sulphate was mostly associated with plasma and 
      perigranular membranes. 5. Chondroitin sulphate appears to be a potent mast cell 
      inhibitor of allergic and nonimmune stimulation with potential clinical 
      implications.
FAU - Theoharides, T C
AU  - Theoharides TC
AD  - Department of Pharmacology and Experimental Therapeutics, Tufts University School 
      of Medicine, 136 Harrison Avenue, Boston, Massachusetts, MA 02111, USA. 
      theoharis.theoharides@tufts.edu
FAU - Patra, P
AU  - Patra P
FAU - Boucher, W
AU  - Boucher W
FAU - Letourneau, R
AU  - Letourneau R
FAU - Kempuraj, D
AU  - Kempuraj D
FAU - Chiang, G
AU  - Chiang G
FAU - Jeudy, S
AU  - Jeudy S
FAU - Hesse, L
AU  - Hesse L
FAU - Athanasiou, A
AU  - Athanasiou A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anti-Asthmatic Agents)
RN  - 9007-28-7 (Chondroitin Sulfates)
RN  - Q2WXR1I0PK (Cromolyn Sodium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Anti-Asthmatic Agents/pharmacology
MH  - Calcium/*metabolism
MH  - Cell Line
MH  - Cell Size/drug effects
MH  - Chondroitin Sulfates/*pharmacology
MH  - Connective Tissue/*drug effects/metabolism
MH  - Cromolyn Sodium/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Histamine Release/*drug effects/physiology
MH  - Humans
MH  - Male
MH  - Mast Cells/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC1572430
EDAT- 2000/11/18 11:00
MHDA- 2001/03/03 10:01
PMCR- 2001/11/01
CRDT- 2000/11/18 11:00
PHST- 2000/11/18 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/11/18 11:00 [entrez]
PHST- 2001/11/01 00:00 [pmc-release]
AID - 0703672 [pii]
AID - 10.1038/sj.bjp.0703672 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2000 Nov;131(6):1039-49. doi: 10.1038/sj.bjp.0703672.