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. 2020 Mar;18(3):528-533.
doi: 10.1111/jth.14724.

Antithrombin: An anticoagulant, anti-inflammatory and antibacterial serpin

Alireza R Rezaie  1   2 , Hemant Giri  1
Affiliations

Antithrombin: An anticoagulant, anti-inflammatory and antibacterial serpin

Alireza R Rezaie et al. J Thromb Haemost. 2020 Mar.
No abstract available

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Conflict of interest statement

Disclosure of Conflict of Interests

The authors declare no conflict of interests.

Figures

Figure 1.
Figure 1.
A hypothetical model for the physiological functions of α and β isoforms of AT. AT circulates in plasma as α-AT (90–95%) and β-AT (5–10%) isoforms. Both isoforms bind heparin via their basic D-helix. The affinity of β-AT for 3-OS containing GAGs including heparin and/or those covalently attached to vascular HSPGs (i.e., Synd-4), is 5–10-fold higher than the affinity of α-AT for the same type of GAGs. Since only a small population of vascular HSPGs contain 3-OS modified GAGs, β-AT preferentially occupies these vascular sites, thereby initiating anti-inflammatory signaling responses through induction of PGI2 synthesis by endothelial cells. Thus, this model predicts that the less abundant β-AT primarily functions as a signaling serpin in endothelial cells and the highly abundant α-AT primarily functions as a coagulation protease inhibitory serpin in circulation. The manuscript by Papareddy et al. has discovered that β-AT also preferentially binds to three cell surface receptor proteins; CD13, CD300f, and LRP-1, on monocytes to initiate anti-inflammatory responses. The mechanism by which β-AT interacts with these receptors has not been investigated. Moreover, since these receptors are glycoproteins, it cannot be ruled out that β-AT interacts via it’s D-helix with carbohydrates attached to these receptors by a mechanism similar to that observed in endothelial cells. Further investigation is required to answer this question. Monocytes are known to also express HSPGs including Synd-4 (not shown). See the text for more details. Figure was prepared by software provided by Biorender.com.
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