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Skoreński et al. Rare Dis Orphan Drugs J 2023;2:6 https://dx.doi.org/10.20517/rdodj.2022.21 Page 3 of 23

Figure 1. Mechanism of action neutrophil serine proteases.

Figure 2. Structure of human neutrophil elastase; (green: Asn95 and Asn144, orange: Arg residues, yellow: disulfide bridges; based on
3Q76.pdb) [16] .

(fibrinogen, factors V, VII, XII, and XIII), plasminogen, immunoglobulins (IgG, IgA, and IgM),
thrombomodulin, platelet, complement factors (C3, C5), complement receptors, and the coat protein of
HIV (gp120) . HNE is also responsible for the degradation or activation of many essential host immune
[15]
molecules, such as interleukins (IL-1β, IL-2, IL-6, IL-8, IL-12p40, and IL-12p70) or tumor necrosis factor.
Furthermore, HNE processes the surface of toll-like receptors TLR2, TLR4, CD14, and tumor necrosis
factor receptors. It can also degrade other neutrophil proteases and proteases inhibitors, resulting in both
their activation and inactivation .
[17]

HNE is an integral component of NETs, which form large web-like structures containing DNA, histones,
and other granular proteins such as proteinase 3, myeloperoxidase, or high mobility group protein B1 .
[18]
NETs play an essential role as a trap for extracellular pathogens in the first-line defense response of the