title: Up-regulation of functional CXCR4 expression on human lymphocytes in sepsis.
abstract: OBJECTIVE
  Lymphocyte dysfunction has been documented in sepsis, and evidence suggests that lymphocyte infiltration contributes to tissue injury. The purpose of this study was to examine chemokine receptor expression and function in lymphocytes from septic patients and healthy donors.
  
  
  METHODS
  Observational study of septic patients and laboratory investigation of normal controls.
  
  
  METHODS
  Tertiary care intensive care unit.
  
  
  METHODS
  Nine critically ill patients fulfilling criteria for the systemic inflammatory response syndrome and with a Sepsis Score of >/=3 were included in this study. Lymphocytes were also obtained from healthy volunteers.
  
  
  METHODS
  None.
  
  
  RESULTS
  The total number of circulating leukocytes in septic patients was markedly increased; however, lymphocyte counts were decreased. Chemokine receptor expression on lymphocytes was examined by flow cytometry. CXCR4 expression on lymphocytes from septic patients was increased whereas CCR5 was decreased and CCR7 was unchanged. Lipopolysaccharide stimulation of normal lymphocytes increased CXCR4 expression but decreased CCR5 and did not change CCR7 expression. This lipopolysaccharide-stimulated CXCR4 expression required 20 hrs of stimulation and was accompanied by increased messenger RNA. Lymphocytes from septic patients or after lipopolysaccharide treatment demonstrated enhanced actin polymerization and migration in response to CXCL12. Taken together, sepsis and lipopolysaccharide up-regulated CXCR4 expression and enhanced lymphocyte activation and migration in response to CXCL12.
  
  
  CONCLUSIONS
  Blocking CXCR4 and CXCL12 function may provide a novel therapeutic method for controlling systemic inflammation and tissue injury in sepsis.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Toronto General Research Institute of the University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Ding
authors.forename: Song H
authors.initials: SH
authors.lastname: Jia
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Downey
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
mesh_terms: D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000096:biosynthesis; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis; D018805:Sepsis / Q000097:blood*
chemical_list: D000199:Actins; C515370:CCR7 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012333:RNA, Messenger; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine