The endoplasmic reticulum stress-mediated apoptosis signal pathway is involved in sepsis-induced abnormal lymphocyte apoptosis.
OBJECTIVE
The mechanisms of abnormal lymphocyte apoptosis in sepsis are only partially defined. The present study was designed to investigate whether the endoplasmic reticulum (ER) is implicated in the extensive apoptosis of lymphocytes in sepsis.


METHODS
C57BL/6 mice were randomized into cecal ligation and puncture (CLP) and sham operation groups. Apoptosis was detected by the TUNEL method and flow cytometry. The expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) was detected by RT-PCR and Western blot. The splicing of X box-binding protein-1 (XBP1) mRNA was detected by RT-PCR.


RESULTS
A high degree of lymphocyte apoptosis was observed in the CLP group. Marked induction of GRP78 and accumulation of spliced XBP1 mRNA were observed in the splenocytes from septic mice, indicating activation of unfolded protein responses. Furthermore, both CHOP and its mRNA were markedly upregulated in the CLP group, suggesting that the ER stress response switched to a proapoptotic response.


CONCLUSIONS
These data demonstrate activation of the unfolded protein response in lymphocytes and that ER stress may contribute to abnormal lymphocyte apoptosis during sepsis. Accordingly, the ER stress-mediated apoptosis pathway may be a novel target in clinical prevention and therapy of sepsis-induced lymphocyte apoptosis.
Department of Surgery, General Hospital, Tianjin Medical University, Tianjin, PR China.
T
T
Ma
L
L
Han
Y
Y
Gao
L
L
Li
X
X
Shang
W
W
Hu
C
C
Xue
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013312:Stress, Physiological / Q000276:immunology; D051742:Transcription Factor CHOP / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D051742:Transcription Factor CHOP