Apoptotic cell recognition receptors and scavenger receptors

Abstract

Summary Phosphatidylserine recognition receptors are a highly diverse set of receptors grouped by their ability to recognize the ‘eat-me’ signal phosphatidylserine on apoptotic cells. Most of the phosphatidylserine recognition receptors dampen inflammation by inducing the production of anti-inflammatory mediators during phagocytosis of apoptotic corpses. However, many phosphatidylserine receptors are also capable of recognizing other ligands, with some receptors being categorized as scavenger receptors. It is now appreciated that these receptors can elicit different downstream events for particular ligands. Therefore, how phosphatidylserine recognition receptors mediate specific signals during recognition of apoptotic cells versus other ligands, and how this might help regulate the inflammatory state of a tissue is an important question that is not fully understood. Here, we revisit the work on signaling downstream of the phosphatidylserine recognition receptor BAI1, and evaluate how these and other signaling modules mediate signaling downstream from other receptors, including Stabilin-2, MerTK and αvβ5. We also propose the concept that phosphatidylserine recognition receptors could be viewed as a subset of scavenger receptors that are capable of eliciting anti-inflammatory responses to apoptotic cells.

MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury

“…Recent reports from independent groups 3 , including our own 4 , implicate efferocytosis (phagocytosis of apoptotic cells) by the macrophage receptor MerTK 5, 6 , as a significant contributor to myocardial repair after experimental MI. The function of MerTK is naturally compromised by its proteolytic cleavage and generation of soluble MER (solMER) 7-9 , which can occur during inflammation and atherosclerosis, and can compromise resolution of both of these processes 8, 10 .…”

CD68/macrosialin: not just a histochemical marker

“…45 CD68 was also considered as a member of the family of SRs as a scavenger receptor type D (SCARD) 46 because (i) CD68 can be significantly upregulated in macrophages responding to inflammatory stimuli; 23,36 (ii) Figure 1 A scheme shows the general features of the domain organization of murine macrosialin and human proteins LAMP-1, LAMP-2, DC-LAMP, and CD68 and depicts the principal differences between the family members. N-glycans and O-glycans are indicated by red and green Ys, respectively.…”

The Dynamics of Apoptotic Cell Clearance

“…A canonical feature of apoptosis is the rapid, caspase-dependent exposure of PtdSer to the outer leaflet of the apoptotic cell plasma membrane. Exposed PtdSer is subsequently recognized by one or more of a cadre of heterogeneous surface receptors expressed on phagocytes (reviewed in (Green et al, 2016; Gregory and Pound, 2010; Hochreiter-Hufford and Ravichandran, 2013; Penberthy and Ravichandran, 2015). However, PtdSer recognition alone is likely not always sufficient to stimulate engulfment, as the duration of PtdSer exposure as well as additional eat-me ligands exposed can work in concert to help the phagocyte properly recognize and engage an apoptotic cell.…”