Up-regulation of functional CXCR4 expression on human lymphocytes in sepsis
Ziqiang Ding1, Song H Jia, John C Marshall
1Division of Thoracic Surgery, Department of Surgery, Toronto General Research Institute of the University Health Network, University of Toronto, Toronto, ON, Canada.
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.
Design:
Observational study of septic patients and laboratory investigation of normal controls.
Setting:
Tertiary care intensive care unit.
Patients And Subjects:
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.
Interventions:
None.
Measurements And Main 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.
