Relationship between HMGB1 content and MHC-II expression in circulating monocytes and spleen of mice challenged with zymosan.
OBJECTIVE
To observe the regularity of change in high mobility group protein box 1 (HMGB1) content in serum and spleen of mice with multiple organ dysfunction syndrome (MODS), to analyze the correlation between HMGB1 content and major histocompatibility complex (MHC)-II---I-A(b) expression on monocytes in blood and spleen, and to explore the effect of HMGB1 on immune function of circulating monocytes and splenocytes.


METHODS
One hundred 8-week-old male 57BL/6 mice were randomly divided into normal group and experimental group subdivided into 8 subgroups: 3, 8, 12 hours, 1, 2, 3, 5-7 days and 10-12 days post zymosan injection (PZI). MODS model was replicated by injecting zymosan into the peritoneal cavity. At each time point, blood and spleen were collected to detect HMGB1 content and the rate of I-A(b) positive monocytes.


RESULTS
In normal and PZI 3-hour, 8-hour mice, serum HMGB1 was not detected, but it significantly increased at PZI 12 hours. In spleen of normal mice, there was low level of HMGB1 expression. In zymosan-treated mice, HMGB1 started to rise in spleen at PZI 3 hours. Subsequently, HMGB1 content in both serum and spleen significantly increased, and it reached the peak level in 1-2 days, decreased in 5 days, and then increased in 10-12 days. The number of I-A(b) positive monocytes in circulating blood and spleen decreased at 1-2 days (t equal to 9.589, 4.432, P <0.01) and 10-12 days following the challenge, forming a two trough like decrease, just corresponding with two-peak increase of HMGB1. However, at 3 hours after zymosan challenge, I-A(b) expression on circulating monocytes was downregulated (t =5.977, P less than 0.01), while that in spleen upregulated (t equal to 4.814, P less than 0.01).


CONCLUSIONS
In mice with MODS, up-regulated HMGB1 expression can regulate I-A(b)expression on monocytes to depress their ability of presenting antigen, which results in immune disturbance contributing development of MODS.
Lü
Yi
Y
Burn Insitute, First Affiliated Hospital of PLA General Hospital, Beijing, China.
Lu
Jiang-yang
JY
Zhao
Min
M
Li
Zhi-hong
ZH
Yang
Yi
Y
D000818:Animals; D024243:HMGB1 Protein / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D009102:Multiple Organ Failure / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology
D024243:HMGB1 Protein; D000949:Histocompatibility Antigens Class II; D015054:Zymosan