PMID- 9767464
OWN - NLM
STAT- MEDLINE
DCOM- 19990128
LR  - 20190512
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 95
IP  - 1
DP  - 1998 Sep
TI  - Inhibition of sCD23 and immunoglobulin E release from human B cells by a 
      metalloproteinase inhibitor, GI 129471.
PG  - 105-10
AB  - Soluble CD23 (sCD23) has been proposed to play an important role in the 
      up-regulation of immunoglobulin E (IgE) synthesis. Production of sCD23 is 
      dependent on the proteolytic cleavage of membrane CD23, but the protease(s) 
      involved in this process remain unknown. Preliminary data, obtained by testing a 
      panel of protease inhibitors, suggested that this enzyme may be a zinc-dependent 
      metalloproteinase. Therefore, we investigated the effect of a standard 
      hydroxamate-type Zn2+ metalloproteinase inhibitor (GI 129471) on both sCD23 and 
      IgE release from human tonsillar B cells, stimulated with interleukin-4 (IL-4) 
      and anti-CD40. Incubation of cells for 3 days with GI 129471 inhibited the 
      production of sCD23 with an IC50 of 602 nm+/-3 nm (n=3), but by 14 days the 
      activity of the compound against sCD23 had decreased by greater than threefold 
      (IC50 2+/-0.26 microM; n=3). On the other hand, GI 129471 caused a potent 
      inhibition of IgE production, with no apparent loss of activity over the culture 
      period (14 days: IC50 250 nm+/-72 nm; n=3). Time-course studies showed that, 
      despite loss of activity against sCD23, inhibition of sCD23 production early in 
      the culture was able to cause a potent and long-lasting inhibitory effect on IgE. 
      Furthermore, we also showed that the activity of GI 129471 is selective for IgE, 
      as no effect was seen on immunoglobulin G1 (IgG1) or IgG4 production at test 
      concentrations as high as 10 microM. These results support the hypothesis that 
      metalloproteinases may be involved in the proteolytic cleavage of CD23 and 
      subsequent regulation of IgE synthesis. Inhibition of the protease(s) responsible 
      for such cleavage may be of value in the treatment of allergic disease.
FAU - Wheeler, D J
AU  - Wheeler DJ
AD  - Department of Cell Biology, Rhone-Poulenc-Rorer Ltd, Dagenham Research Centre, 
      Dagenham, Essex, UK.
FAU - Parveen, S
AU  - Parveen S
FAU - Pollock, K
AU  - Pollock K
FAU - Williams, R J
AU  - Williams RJ
LA  - eng
PT  - Journal Article
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulin Isotypes)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Receptors, IgE)
RN  - 130370-59-1 (GI 129471)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - B-Lymphocytes/*drug effects/*immunology
MH  - Cells, Cultured
MH  - Depression, Chemical
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - *Immunoglobulin E
MH  - Immunoglobulin G
MH  - Immunoglobulin Isotypes
MH  - Interleukin-4/pharmacology
MH  - Metalloendopeptidases/*antagonists & inhibitors
MH  - Palatine Tonsil/immunology
MH  - Phenylalanine/*analogs & derivatives/pharmacology
MH  - Protease Inhibitors/*pharmacology
MH  - *Receptors, IgE
MH  - Time Factors
PMC - PMC1364383
EDAT- 1998/10/10 00:00
MHDA- 1998/10/10 00:01
PMCR- 1999/09/01
CRDT- 1998/10/10 00:00
PHST- 1998/10/10 00:00 [pubmed]
PHST- 1998/10/10 00:01 [medline]
PHST- 1998/10/10 00:00 [entrez]
PHST- 1999/09/01 00:00 [pmc-release]
AID - 10.1046/j.1365-2567.1998.00578.x [doi]
PST - ppublish
SO  - Immunology. 1998 Sep;95(1):105-10. doi: 10.1046/j.1365-2567.1998.00578.x.