PMID- 16506286
OWN - NLM
STAT- MEDLINE
DCOM- 20060413
LR  - 20220129
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 36
IP  - 3
DP  - 2006 Mar
TI  - Expression and alternative processing of IL-18 in human neutrophils.
PG  - 722-31
AB  - Interleukin-18 (IL-18), a member of the IL-1 cytokine superfamily, is an 
      important regulator of both innate and acquired immune responses. We demonstrate 
      here constitutive expression of IL-18 by human neutrophils. Unexpectedly, we 
      observed that neutrophils from peripheral blood or rheumatoid synovial 
      compartments contained not only pro and mature IL-18, but also several novel 
      smaller-molecular-weight IL-18-derived species. Using specific protease 
      inhibitors, and serine protease gene-targeted mice, we demonstrate that these 
      IL-18-derived products arose through caspase-independent cleavage events mediated 
      by the serine proteases, elastase and cathepsin G. Moreover, we report that the 
      net effect of elastase treatment of mature recombinant IL-18 was to reduce its 
      IFN-gamma-inducing activity. Thus, human neutrophils contain IL-18 and 
      IL-18-derived molecular species that can arise through novel enzymatic processing 
      pathways. Through cytosolic, membrane or secretory expression of such processing 
      enzymes, together with generation of IL-18 itself, neutrophils likely play a 
      critical role in regulating IL-18 activities during early innate immune 
      responses.
FAU - Robertson, Susan E
AU  - Robertson SE
AD  - CRD, Division of Immunology, Infection & Inflammation, Glasgow Royal Infirmary, 
      Glasgow, UK.
FAU - Young, John D
AU  - Young JD
FAU - Kitson, Susan
AU  - Kitson S
FAU - Pitt, Andrew
AU  - Pitt A
FAU - Evans, Jamie
AU  - Evans J
FAU - Roes, Jurgen
AU  - Roes J
FAU - Karaoglu, Denise
AU  - Karaoglu D
FAU - Santora, Ling
AU  - Santora L
FAU - Ghayur, Tariq
AU  - Ghayur T
FAU - Liew, Foo Y
AU  - Liew FY
FAU - Gracie, J Alastair
AU  - Gracie JA
FAU - McInnes, Iain B
AU  - McInnes IB
LA  - eng
GR  - G9818261/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Interleukin-18)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Humans
MH  - Immunity, Innate/*immunology
MH  - Interferon-gamma/immunology
MH  - Interleukin-18/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Neutrophil Activation/genetics/*immunology
MH  - Neutrophils/enzymology/*immunology
MH  - Peptide Hydrolases/deficiency/immunology
MH  - Protein Processing, Post-Translational/*immunology
MH  - Secretory Vesicles/enzymology/*immunology
EDAT- 2006/03/01 09:00
MHDA- 2006/04/14 09:00
CRDT- 2006/03/01 09:00
PHST- 2006/03/01 09:00 [pubmed]
PHST- 2006/04/14 09:00 [medline]
PHST- 2006/03/01 09:00 [entrez]
AID - 10.1002/eji.200535402 [doi]
PST - ppublish
SO  - Eur J Immunol. 2006 Mar;36(3):722-31. doi: 10.1002/eji.200535402.