PMID- 26168217
OWN - NLM
STAT- MEDLINE
DCOM- 20151023
LR  - 20181113
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 125
IP  - 8
DP  - 2015 Aug 3
TI  - T lymphocytes and fractalkine contribute to myocardial ischemia/reperfusion 
      injury in patients.
PG  - 3063-76
LID - 80055 [pii]
LID - 10.1172/JCI80055 [doi]
AB  - BACKGROUND: Lymphocytes contribute to ischemia/reperfusion (I/R) injury in 
      several organ systems, but their relevance in ST elevation myocardial infarction 
      (STEMI) is unknown. Our goal was to characterize lymphocyte dynamics in 
      individuals after primary percutaneous coronary intervention (PPCI), assess the 
      prognostic relevance of these cells, and explore mechanisms of 
      lymphocyte-associated injury. METHODS: Lymphocyte counts were retrospectively 
      analyzed in 1,377 STEMI patients, and the prognostic relevance of post-PPCI 
      lymphopenia was assessed by Cox proportional hazards regression. Blood from 59 
      prospectively recruited STEMI patients undergoing PPCI was sampled, and leukocyte 
      subpopulations were quantified. Microvascular obstruction (MVO), a component of 
      I/R injury, was assessed using MRI. RESULTS: In the retrospective cohort, 
      lymphopenia was associated with a lower rate of survival at 3 years (82.8% vs. 
      96.3%, lowest vs. highest tertile; hazard ratio 2.42). In the prospective cohort, 
      lymphocyte counts fell 90 minutes after reperfusion, primarily due to loss of T 
      cells. CD8+ T cells decreased more than CD4+ T cells, and effector subsets 
      exhibited the largest decline. The early decrease in effector T cell levels was 
      greater in individuals that developed substantial MVO. The drop in T cell subsets 
      correlated with expression of the fractalkine receptor CX3CR1 (r2 = 0.99, P = 
      0.006). Serum fractalkine concentration peaked at 90 minutes after reperfusion, 
      coinciding with the T cell count nadir. CONCLUSIONS: Lymphopenia following PPCI 
      is associated with poor prognosis. Our data suggest that fractalkine contributes 
      to lymphocyte shifts, which may influence development of MVO through the action 
      of effector T cells. TRIAL REGISTRATION: Not applicable. FUNDING: British Heart 
      Foundation (FS/12/31/29533) and National Institute of Health Research (NIHR) 
      Newcastle Biomedical Research Centre.
FAU - Boag, Stephen E
AU  - Boag SE
FAU - Das, Rajiv
AU  - Das R
FAU - Shmeleva, Evgeniya V
AU  - Shmeleva EV
FAU - Bagnall, Alan
AU  - Bagnall A
FAU - Egred, Mohaned
AU  - Egred M
FAU - Howard, Nicholas
AU  - Howard N
FAU - Bennaceur, Karim
AU  - Bennaceur K
FAU - Zaman, Azfar
AU  - Zaman A
FAU - Keavney, Bernard
AU  - Keavney B
FAU - Spyridopoulos, Ioakim
AU  - Spyridopoulos I
LA  - eng
GR  - FS/12/31/29533/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150713
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (CX3CL1 protein, human)
RN  - 0 (Chemokine CX3CL1)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - CD4 Lymphocyte Count
MH  - CD4-Positive T-Lymphocytes/*metabolism/pathology
MH  - CD8-Positive T-Lymphocytes/*metabolism/pathology
MH  - Chemokine CX3CL1/*blood
MH  - Female
MH  - Humans
MH  - *Lymphopenia/blood/etiology/mortality
MH  - Male
MH  - Middle Aged
MH  - *Myocardial Infarction/blood/complications/mortality
MH  - *Myocardial Reperfusion Injury/blood/complications/mortality
MH  - Retrospective Studies
MH  - Survival Rate
PMC - PMC4563749
EDAT- 2015/07/15 06:00
MHDA- 2015/10/24 06:00
PMCR- 2015/11/03
CRDT- 2015/07/14 06:00
PHST- 2014/11/17 00:00 [received]
PHST- 2015/05/28 00:00 [accepted]
PHST- 2015/07/14 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2015/10/24 06:00 [medline]
PHST- 2015/11/03 00:00 [pmc-release]
AID - 80055 [pii]
AID - 10.1172/JCI80055 [doi]
PST - ppublish
SO  - J Clin Invest. 2015 Aug 3;125(8):3063-76. doi: 10.1172/JCI80055. Epub 2015 Jul 
      13.