Sepsis and ARDS: The Dark Side of Histones

Table 2

Current evidence of targeting extracellular histones for therapy.

Antibody or molecule	Mechanism	References
SSV mAb	Bind to H1; cross-reactivity against H3, H4	[93]
LG2-1	Neutralize H3	[18, 35, 86, 92]
LG2-2	Neutralize H2B	[18, 35, 86, 92]
BWA3	Neutralize H2A and H4	[18, 35, 86, 92]
Anti-TLR2/TLR4/TLR9	Blockade of TLR2/TLR4/TLR9 receptors	[30, 37, 38]
Heparin	Negative charge	[89, 90]
Albumin	Negative charge	[66]
CRP	Negative charge	[94, 99]
SAP	Negative charge	[99]
P33	Negative charge	[72]
IAIP	Negative charge	[73]
HMW-HA	Negative charge	[73, 95]
PTX3	Coaggregation with histones	[96]
rTM	Inhibit histone-induced platelet aggregation	[68]
APC	Degrade histones	[16, 30, 86, 98]

TLR = toll-like receptor, CRP = C-reactive protein, SAP = serum amyloid P component, P33 = endothelial surface protein/gC1q receptor, IAIP = interalpha inhibitor protein, HMW-HA = high molecular weight hyaluronan, PTX3 = pentraxin 3, rTM = recombinant thrombomodulin, and APC = active protein C.