PMID- 11166285
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 412
IP  - 3
DP  - 2001 Feb 2
TI  - The activation of synovial mast cells: modulation of histamine release by 
      tryptase and chymase and their inhibitors.
PG  - 223-9
AB  - Mast cells have been implicated as having pivotal roles in arthritis, but little 
      is known of the processes leading to the activation of synovial mast cells or 
      their potential for pharmacological control. We have investigated the ability of 
      tryptase and chymase, and inhibitors of these major mast cell proteases to 
      modulate the activation of mast cells from human synovial tissue. The tryptase 
      inhibitor drug N-(1-hydroxy-2-naphthoyl)-L-arginyl-L-prolinamide hydrochloride 
      (APC366) inhibited immunoglobulin E (IgE)-dependent histamine release in a 
      dose-dependent manner, with about 70% inhibition being achieved at a dose of 300 
      microM. Histamine release stimulated by calcium ionophore A23187 was also 
      inhibited by this compound. The chymase inhibitor chymostatin inhibited 
      IgE-dependent histamine release by approximately 60% at 1 microg/ml. Tryptase at 
      concentrations of 3.0 microg/ml and greater stimulated histamine release from 
      synovial cells, which was dependent on catalytic activity, whereas chymase had 
      little effect on these cells. The activation of mast cells by tryptase may 
      represent an amplification process in the synovium. The mast cell stabilising 
      properties of inhibitors of tryptase and chymase could be of therapeutic value in 
      arthritis.
FAU - He, S
AU  - He S
AD  - Immunopharmacology Group, University of Southampton, South Block, Southampton 
      General Hospital, Mailpoint 837, SO16 6YD, Southampton, UK.
FAU - Gaca, M D
AU  - Gaca MD
FAU - Walls, A F
AU  - Walls AF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Dipeptides)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Ionophores)
RN  - 0 (N-(1-hydroxy-2-naphthoyl)arginyl-prolinamide)
RN  - 0 (Oligopeptides)
RN  - 0 (Serine Proteinase Inhibitors)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 9076-44-2 (chymostatin)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.39 (Chymases)
RN  - EC 3.4.21.59 (Tryptases)
SB  - IM
MH  - Calcimycin/pharmacology
MH  - Chymases
MH  - Dipeptides/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Histamine Release/drug effects/*physiology
MH  - Humans
MH  - Immunoglobulin E/metabolism
MH  - Inflammation Mediators/antagonists & inhibitors/isolation & 
      purification/*metabolism
MH  - Ionophores/pharmacology
MH  - Mast Cells/*drug effects/*enzymology/immunology/physiology
MH  - Oligopeptides/pharmacology
MH  - Serine Endopeptidases/isolation & purification/*metabolism
MH  - Serine Proteinase Inhibitors/pharmacology
MH  - Synovial Membrane/*cytology/metabolism
MH  - Tryptases
EDAT- 2001/02/13 11:00
MHDA- 2001/05/22 10:01
CRDT- 2001/02/13 11:00
PHST- 2001/02/13 11:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/02/13 11:00 [entrez]
AID - S0014299901007348 [pii]
AID - 10.1016/s0014-2999(01)00734-8 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2001 Feb 2;412(3):223-9. doi: 10.1016/s0014-2999(01)00734-8.