1. Sickle cell disease increases high mobility group box 1: a novel mechanism of inflammation
by Hao Xu, Nancy J. Wandersee, YiHe Guo, Deron W. Jones, Sandra L. Holzhauer, Madelyn S. Hanson, Evans Machogu, David C. Brousseau, Neil Hogg, John C. Densmore, Sushma Kaul, Cheryl A. Hillery, and Kirkwood A. Pritchard
Blood
Volume 124(26):
December 18, 2014
©2014 by American Society of Hematology

2. SCD increases plasma HMGB1 and TLR4 receptor activity in humans.
SCD increases plasma HMGB1 and TLR4 receptor activity in humans. (A) Plasma concentrations of HMGB1 in control and SCD individuals (n = 19, 26, respectively, **P = .047); (B) HMGB1 concentrations in plasma from SCD individuals at baseline and crisis (n = 19, *P = .0362); (C) Total TLR4 receptor activity induced by control and SCD plasma (n = 12, *P < .05, ***P < .01); (D) HMGB1-dependent TLR4 receptor activity in plasma from SCD individuals at baseline and crisis. Data represent TLR4 reporter cell activity inhibited by pretreating plasma with anti-HMGB1 antibodies (n = 12, *P < .05); and (E) HMGB1-dependent TLR4 receptor activity represented as a percentage of total TLR4 receptor activity (n = 11 to 12, ***P < .01).
Hao Xu et al. Blood 2014;124:
©2014 by American Society of Hematology

3. HMGB1 levels, TLR4 receptor activity, and HMGB1-dependent TLR4 receptor activity are increased in mice with SCD. (A) Plasma HMGB1 levels in SCD (SS) (hatched bar) compared with control (black bar, n = 9, 11, **P < .01) mice; (B) Plasma-induced total TLR4 re...
HMGB1 levels, TLR4 receptor activity, and HMGB1-dependent TLR4 receptor activity are increased in mice with SCD. (A) Plasma HMGB1 levels in SCD (SS) (hatched bar) compared with control (black bar, n = 9, 11, **P < .01) mice; (B) Plasma-induced total TLR4 receptor activity is increased in SS (hatched bar) compared with control (black bar, n = 6, *P < .05) mice; (C) % HMGB1-dependent TLR4 receptor activity in SS (hatched bar) compared with control (black bar, n = 6, *P < .05) mice; (D) Effect of H/R injury (see Study design) on HMGB1 levels. Left bars: control normoxia (open bar, n = 13) vs control H/R (gray open bar, n = 7) mice; NS, not significant. Right bars: SS normoxia (right-hatched open bar, n = 20) vs SS H/R (left-hatched gray bar, n = 17) mice (*P < .05); (E) Pretreatment of SS mice with isotype control (black bar) or anti-HMGB1 (hatched bar) antibodies did not significantly decrease HMGB1 levels (P = .095, n = 14 to 15); (F) Pretreatment of SS mice with anti-HMGB1 (hatched bar) but not isotype control (black bar) antibodies significantly decreases the ability of SS plasma to induce total TLR4 receptor activity in cultured TLR4 reporter cells (n = 6, *P < .05); and (G) Pretreatment of SS mice with anti-HMGB1 (hatched bar) but not isotype control (black bar) antibodies significantly decreased the % of HMGB1-dependent TLR4 receptor activity in SS plasma (n = 6, *P < .05).
Hao Xu et al. Blood 2014;124:
©2014 by American Society of Hematology