Regulation of the Complement System by Pentraxins

Abstract

The functions of pentraxins, like C-reactive protein (CRP), serum amyloid protein P (SAP) and pentraxin-3 (PTX3), are to coordinate spatially and temporally targeted clearance of injured tissue components, to protect against infections and to regulate related inflammation together with the complement system. For this, pentraxins have a dual relationship with the complement system. Initially, after a focused binding to their targets, e.g., exposed phospholipids or cholesterol in the injured tissue area, or microbial components, the pentraxins activate complement by binding its first component C1q. However, the emerging inflammation needs to be limited to the target area. Therefore, pentraxins inhibit complement at the C3b stage to prevent excessive damage. The complement inhibitory functions of pentraxins are based on their ability to interact with complement inhibitors C4bp or factor H (FH). C4bp binds to SAP, while FH binds to both CRP and PTX3. FH promotes opsonophagocytosis through inactivation of C3b to iC3b, and inhibits AP activity thus preventing formation of the C5a anaphylatoxin and the complement membrane attack complex (MAC). Monitoring CRP levels gives important clinical information about the extent of tissue damage and severity of infections. CRP is a valuable marker for distinguishing bacterial infections from viral infections. Disturbances in the functions and interactions of pentraxins and complement are also involved in a number of human diseases. This review will summarize what is currently known about the FH family proteins and pentraxins that interact with FH. Furthermore, we will discuss diseases, where interactions between these molecules may play a role.

Predictive value of pentraxin-3 on disease severity and prognosis in patients with hemorrhagic fever with renal syndrome

“…Pentraxin-3 synthesized by neutrophils is mainly stored in neutrophil granules, which can interact with a variety of bacteria, fungi and viruses after release and then propel the phagocytosis and clearance of pathogenic microorganisms [21]. As an important component of innate humoral immunity, pentraxin-3 has the ability to bind complement component C1q and then activate the classical pathway of complement [22,23]. Recently, many studies have showed that pentraxin-3 could modulate in ammatory cells, interact with P-selectin, reduce the nitric oxide (NO) synthesis of endothelial cells, inhibit endothelial cells proliferation and alter their functions, and nally promote vascular in ammatory response and endothelial dysfunction [24,25].…”

Predictive value of pentraxin-3 on disease severity and prognosis in patients with hemorrhagic fever with renal syndrome

“…Pentraxin-3 synthesized by neutrophils is mainly stored in neutrophil granules, which can interact with a variety of bacteria, fungi and viruses after release and then propel the phagocytosis and clearance of pathogenic microorganisms [19]. As an important component of innate humoral immunity, pentraxin-3 has the ability to bind complement component C1q and then activate the classical pathway of complement [20,21]. Recently, many studies have showed that pentraxin-3 could modulate in ammatory cells, interact with P-selectin, reduce the nitric oxide (NO) synthesis of endothelial cells, inhibit endothelial cells proliferation and alter their functions, and nally promote vascular in ammatory response and endothelial dysfunction [22,23].…”

The complement system in Aspergillus fumigatus infections and its crosstalk with pentraxins

“…The following sections focus on pentraxins, particularly the long pentraxin PTX3 (see Ref. [97] for a review on complement regulation by pentraxins).…”