PMID- 10792365
OWN - NLM
STAT- MEDLINE
DCOM- 20000821
LR  - 20220310
IS  - 0954-7894 (Print)
IS  - 0954-7894 (Linking)
VI  - 30
IP  - 5
DP  - 2000 May
TI  - Inhibition of CD23 processing correlates with inhibition of IL-4-stimulated IgE 
      production in human PBL and hu-PBL-reconstituted SCID mice.
PG  - 719-27
AB  - BACKGROUND: CD23, the low affinity serum immunoglobulin E (IgE) receptor, is 
      upregulated on B cells following interleukin (IL)-4 stimulation and is 
      concomitantly cleaved to generate soluble CD23 (sCD23) fragments with 
      cytokine-like activity. OBJECTIVE: Compounds that selectively inhibit the 
      proteolytic release of CD23 to generate sCD23 were assessed for their ability to 
      inhibit IgE production in order to evaluate the contribution of sCD23 in the 
      production of human IgE as well as the ability of such compounds to block IgE 
      production. METHODS: IgE production was measured in IL-4-stimulated human 
      peripheral blood lymphocytes (PBL) and PBL-reconstituted SCID mice in the 
      presence of a broad-spectrum matrix metalloprotease (MMP) inhibitor, a compound 
      selective for inhibition of CD23 processing over MMPs and an anti-CD23 mAb, MHM6. 
      RESULTS: The two compounds were equipotent in inhibiting IgE production without 
      inhibition of IgG production by IL-4/anti-CD40-stimulated PBL. Soluble CD23 
      release was also shown to precede IgE accumulation in the cell-free medium. 
      Addition of compound at later times other than day 0 in the 14 day assay resulted 
      in progressively less inhibition of both IgE and sCD23, and exactly paralleled 
      the effect of an anti-CD23 mAb, MHM6 on IgE levels. Both compounds also inhibited 
      the release of CD23 from human RPMI 8866 cells adoptively transferred i. p. to 
      mice. Doses required for inhibition of CD23 correlated well with the doses 
      required for inhibition of IgE production in IL-4-challenged hu-PBL-SCID mice. 
      IgE was selectively inhibited over total IgG in the SCID mice as well. 
      CONCLUSIONS: Inhibition of CD23 processing alone is sufficient to inhibit 
      IL-4-stimulated IgE production both in vitro and in vivo.
FAU - Mayer, R J
AU  - Mayer RJ
AD  - Department of Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 
      19406, USA.
FAU - Bolognese, B J
AU  - Bolognese BJ
FAU - Al-Mahdi, N
AU  - Al-Mahdi N
FAU - Cook, R M
AU  - Cook RM
FAU - Flamberg, P L
AU  - Flamberg PL
FAU - Hansbury, M J
AU  - Hansbury MJ
FAU - Khandekar, S
AU  - Khandekar S
FAU - Appelbaum, E
AU  - Appelbaum E
FAU - Faller, A
AU  - Faller A
FAU - Marshall, L A
AU  - Marshall LA
LA  - eng
PT  - Journal Article
PL  - England
TA  - Clin Exp Allergy
JT  - Clinical and experimental allergy : journal of the British Society for Allergy 
      and Clinical Immunology
JID - 8906443
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, IgE)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
CIN - Clin Exp Allergy. 2000 May;30(5):602-5. PMID: 10792350
MH  - Animals
MH  - Chimera
MH  - Enzyme Inhibitors/*pharmacology
MH  - Humans
MH  - Immunoglobulin E/*biosynthesis
MH  - Immunosuppressive Agents/*pharmacology
MH  - Interleukin-4/*antagonists & inhibitors/*physiology
MH  - Lymphocyte Transfusion
MH  - Lymphocytes/drug effects/immunology/*metabolism
MH  - Matrix Metalloproteinase Inhibitors
MH  - Mice
MH  - Mice, SCID
MH  - Peptide Fragments/antagonists & inhibitors/metabolism
MH  - Protein Processing, Post-Translational/drug effects/*immunology
MH  - Receptors, IgE/*antagonists & inhibitors/metabolism
MH  - Solubility
EDAT- 2000/05/03 09:00
MHDA- 2000/08/29 11:01
CRDT- 2000/05/03 09:00
PHST- 2000/05/03 09:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/05/03 09:00 [entrez]
AID - cea812 [pii]
AID - 10.1046/j.1365-2222.2000.00812.x [doi]
PST - ppublish
SO  - Clin Exp Allergy. 2000 May;30(5):719-27. doi: 10.1046/j.1365-2222.2000.00812.x.