PMID- 11298826
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20190513
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 102
IP  - 3
DP  - 2001 Mar
TI  - Metalloprotease inhibitor-mediated inhibition of mouse immunoglobulin production.
PG  - 281-8
AB  - High levels of membrane CD23 have been shown to decrease immunoglobulin E (IgE). 
      CD23 is a very labile molecule and is cleaved from the cell surface by an unknown 
      metalloprotease. Two metalloprotease inhibitors, compound A 
      (N-[4-hydoxyamino-2-(R)-isobutyl-3-(S)propargylthiomethylsuccinyl]-(S)-phenylalnine-N'-methyl-amide) 
      and compound B (N-[3-(S)-hydroxy-4-hydroxyamino-2-(R)-(2-naphthylmethyl) 
      succinyl]-(S)-tert-leucinamide), were chosen for their ability to inhibit human 
      CD23 cleavage and selectively inhibit IgE production. The ability of these 
      inhibitors to block cleavage of murine CD23 and immunoglobulin production in an 
      in vitro system was examined. The inhibitors blocked sCD23 release from B cells. 
      The inhibitors also decreased IgE production by B cells; however, 20-30 times 
      more inhibitor was needed to give a similar amount of inhibition as compared with 
      sCD23 release. The effects on immunoglobulin production did not require the 
      presence of CD23 in that these inhibitors also blocked in vitro immunoglobulin 
      production when B cells from CD23-/- mice were used. The inhibitors decreased 
      production of all other immunoglobulin isotypes examined and reduced the number 
      of IgE antibody-forming cells (AFC) while having no effect on cell proliferation 
      or viability. The level of Iepsilon transcripts in cells treated with compounds A 
      and B were not different as compared with control cells. These results suggest 
      that while these inhibitors effectively inhibit IgE production in a CD23-specific 
      manner in the human, these compounds, in the mouse, inhibit immunoglobulin 
      production by an unknown mechanism that is unrelated to CD23.
FAU - Kilmon, M A
AU  - Kilmon MA
AD  - Virginia Commonwealth University, Department of Microbiology and Immunology, 
      Richmond, VA 23298, USA. mkilmon@hsc.vcu.edu
FAU - Mayer, R J
AU  - Mayer RJ
FAU - Marshall, L A
AU  - Marshall LA
FAU - Conrad, D H
AU  - Conrad DH
LA  - eng
GR  - R01 AI018697/AI/NIAID NIH HHS/United States
GR  - AI44163/AI/NIAID NIH HHS/United States
GR  - R01 AI044163/AI/NIAID NIH HHS/United States
GR  - T32 AI007407/AI/NIAID NIH HHS/United States
GR  - AI18697/AI/NIAID NIH HHS/United States
GR  - AI07407/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (CH3OCF2CH(CF3)OCH2F)
RN  - 0 (Ethers)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Receptors, IgE)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 58109-34-5 (fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/immunology
MH  - Cell Culture Techniques
MH  - Dose-Response Relationship, Immunologic
MH  - Ethers/pharmacology
MH  - Humans
MH  - Hydrocarbons, Fluorinated/pharmacology
MH  - Immunoglobulin E/*biosynthesis
MH  - Immunoglobulin G/biosynthesis
MH  - Immunoglobulin M/biosynthesis
MH  - Metalloendopeptidases/*antagonists & inhibitors
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Protease Inhibitors/*pharmacology
MH  - Receptors, IgE/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription, Genetic/drug effects
PMC - PMC1783188
EDAT- 2001/04/12 10:00
MHDA- 2001/05/22 10:01
PMCR- 2002/03/01
CRDT- 2001/04/12 10:00
PHST- 2001/04/12 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/04/12 10:00 [entrez]
PHST- 2002/03/01 00:00 [pmc-release]
AID - imm1188 [pii]
AID - 10.1046/j.1365-2567.2001.01188.x [doi]
PST - ppublish
SO  - Immunology. 2001 Mar;102(3):281-8. doi: 10.1046/j.1365-2567.2001.01188.x.