PMID- 20956350
OWN - NLM
STAT- MEDLINE
DCOM- 20101202
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 185
IP  - 10
DP  - 2010 Nov 15
TI  - Domain V peptides inhibit beta2-glycoprotein I-mediated mesenteric 
      ischemia/reperfusion-induced tissue damage and inflammation.
PG  - 6168-78
LID - 10.4049/jimmunol.1002520 [doi]
AB  - Reperfusion of ischemic tissue induces significant tissue damage in multiple 
      conditions, including myocardial infarctions, stroke, and transplantation. 
      Although not as common, the mortality rate of mesenteric ischemia/reperfusion 
      (IR) remains >70%. Although complement and naturally occurring Abs are known to 
      mediate significant damage during IR, the target Ags are intracellular molecules. 
      We investigated the role of the serum protein, beta2-glycoprotein I as an initiating 
      Ag for Ab recognition and beta2-glycoprotein I (beta2-GPI) peptides as a therapeutic 
      for mesenteric IR. The time course of beta2-GPI binding to the tissue indicated 
      binding and complement activation within 15 min postreperfusion. Treatment of 
      wild-type mice with peptides corresponding to the lipid binding domain V of 
      beta2-GPI blocked intestinal injury and inflammation, including cellular influx and 
      cytokine and eicosanoid production. The optimal therapeutic peptide (peptide 296) 
      contained the lysine-rich region of domain V. In addition, damage and most 
      inflammation were also blocked by peptide 305, which overlaps with peptide 296 
      but does not contain the lysine-rich, phospholipid-binding region. Importantly, 
      peptide 296 retained efficacy after replacement of cysteine residues with serine. 
      In addition, infusion of wild-type serum containing reduced levels of anti-beta2-GPI 
      Abs into Rag-1(-/-) mice prevented IR-induced intestinal damage and inflammation. 
      Taken together, these data suggest that the serum protein beta2-GPI initiates the 
      IR-induced intestinal damage and inflammatory response and as such is a critical 
      therapeutic target for IR-induced damage and inflammation.
FAU - Fleming, Sherry D
AU  - Fleming SD
AD  - Division of Biology, Kansas State University, Manhattan, KS 66506, USA. 
      sdflemin@ksu.edu
FAU - Pope, Michael R
AU  - Pope MR
FAU - Hoffman, Sara M
AU  - Hoffman SM
FAU - Moses, Tiffany
AU  - Moses T
FAU - Bukovnik, Urska
AU  - Bukovnik U
FAU - Tomich, John M
AU  - Tomich JM
FAU - Wagner, Lynn M
AU  - Wagner LM
FAU - Woods, Keith M
AU  - Woods KM
LA  - eng
GR  - P20 RR017686/RR/NCRR NIH HHS/United States
GR  - RR016475/RR/NCRR NIH HHS/United States
GR  - R01 AI061691-04/AI/NIAID NIH HHS/United States
GR  - AI061691/AI/NIAID NIH HHS/United States
GR  - P20 RR017686-09/RR/NCRR NIH HHS/United States
GR  - P20 RR016475/RR/NCRR NIH HHS/United States
GR  - P20 RR016475-10/RR/NCRR NIH HHS/United States
GR  - R01 AI061691/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101018
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (beta 2-Glycoprotein I)
SB  - IM
MH  - Animals
MH  - Immunohistochemistry
MH  - Immunoprecipitation
MH  - Inflammation/immunology/*metabolism
MH  - Intestinal Mucosa/metabolism
MH  - Mesentery/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Reperfusion Injury/*metabolism/pathology
MH  - beta 2-Glycoprotein I/*metabolism
PMC - PMC3001127
MID - NIHMS254926
COIS- The authors have no conflicting financial interests.
EDAT- 2010/10/20 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/11/15
CRDT- 2010/10/20 06:00
PHST- 2010/10/20 06:00 [entrez]
PHST- 2010/10/20 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/11/15 00:00 [pmc-release]
AID - jimmunol.1002520 [pii]
AID - 10.4049/jimmunol.1002520 [doi]
PST - ppublish
SO  - J Immunol. 2010 Nov 15;185(10):6168-78. doi: 10.4049/jimmunol.1002520. Epub 2010 
      Oct 18.