Class A scavenger receptor-mediated cell adhesion requires the sequential activation of Lyn and PI3-kinase

Nikolic, Dejan; Cholewa, Jill; Gass, Cecelia; Gong, Ming; Post, Steven R.

doi:10.1152/ajpcell.00401.2006

Cited by 38 publications

(50 citation statements)

References 32 publications

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“…by guest www.bloodjournal.org From insensitive to Src inhibition by PP2. 53 Although the prophagocytic receptors involved may differ, the signal transduction events found to be important for uptake of Ox-RBCs by RPM in the present study are in agreement with that described for uptake of apoptotic T cells by the same macrophage population. 54 In conclusion, our findings extend the previous knowledge on CD47 and its function to inhibit phagocytosis of RBCs, to also include experimentally senescent RBCs.…”

Section: Role Of Cd47 In Phagocytosis Of Senescent Rbcs 4265supporting

confidence: 91%

CD47 on experimentally senescent murine RBCs inhibits phagocytosis following Fcγ receptor–mediated but not scavenger receptor–mediated recognition by macrophages

Olsson

Oldenborg

2008

Blood

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IntroductionRemoval of senescent red blood cells (RBCs) from the circulation is a selective process mediated mainly by macrophages in the liver and spleen. 1 Several molecular patterns, which may be involved as ligands in recognition by macrophages, appear on the surface of senescent RBCs. Macrophages can either directly recognize these ligands, or recognition can be dependent on binding of bridging plasma proteins that may interact with the RBC ligands. [2][3][4][5][6][7] As such, these RBC ligands may include alterations in protein carbohydrate moieties, 8 loss of plasma membrane phospholipid asymmetry, [9][10][11] and/or clustering of Band 3 with subsequent binding of complement or antibodies. 12-14 Phagocytosis by macrophages can for instance be induced following ligation of receptors such as Fc␥ receptors (Fc␥R), complement receptors, or scavenger receptors (SRs). [15][16][17] Fc␥R recognizes the Fc portion of immunoglobulin G (IgG) bound to a target cell, resulting in rapid phagocytosis of the IgG-opsonized target. SRs make up a large family of receptors with a broad ligand-binding ability, where most known ligands are polyanionic molecules such as proteins, polyribonucleotides, polysaccharides, and lipids. 16 "Altered" host molecules (eg, oxidized low-density lipoprotein [oxLDL]) can be recognized by most SRs, whereas other ligands interact more specifically with SRs. 16 Oxidative damage is likely to be one important cause of RBC senescence and exposure of senescence-associated ligands. 13,18 RBCs oxidized in vitro (Ox-RBCs) are efficiently phagocytosed by macrophages in the absence of further opsonization, a process shown to be inhibited by oxLDL or other SR ligands, such as fucoidan, dextran sulfate, or poly-I, both in vivo and in vitro. 4,7,19 Phagocytosis of Ox-RBCs has also been suggested to be serum dependent, 6 and involve recognition of phosphatidylserine (PS) on the RBC surface. 9,10 Macrophage phagocytosis of target host cells is regulated by the balance between signaling through prophagocytic receptors (eg, Fc␥R or complement receptors) and inhibitory receptors. Recognition of the cell surface glycoprotein CD47 by the inhibitory receptor signal regulatory protein alpha (SIRP␣) inhibits phagocytosis of unopsonized RBCs, as well as IgG or complementopsonized RBCs, both in vivo and in vitro. 20-23 CD47 is highly expressed on RBCs, but ubiquitously expressed by most cells in the body, and can also negatively regulate phagocytosis of platelets and leukocytes. [24][25][26] The amount of CD47 on the cell surface regulates macrophage phagocytosis, since IgG-opsonized RBCs from CD47 ϩ/Ϫ mice (expressing about 50% of normal levels of CD47) are taken up faster than wild-type (WT) RBCs, but slower than CD47 Ϫ/Ϫ RBCs. 27 We have shown that the phagocytosis-inhibitory effect of CD47 does not come into play on apoptotic nucleated cells, where CD47 is clustered into patches on the apoptotic cell surface and segregated away from prophagocytic ligands such as PS or calreticulin. 25 Although older circulating RBC...

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Section: Role Of Cd47 In Phagocytosis Of Senescent Rbcs 4265supporting

confidence: 91%

CD47 on experimentally senescent murine RBCs inhibits phagocytosis following Fcγ receptor–mediated but not scavenger receptor–mediated recognition by macrophages

Olsson

Oldenborg

2008

Blood

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“…Post et al showed that class A scavenger receptor–mediated cell adhesion activates pertussistoxin–sensitive Gi/o proteins and formation of focal adhesion complexes by mouse peritoneal macrophages. 136 Nikolic et al 137 confirmed the results of Post et al 136 showing that SR-A–dependent adhesion was via activation of Gi/o protein. Nikolic et al further showed that SR-A–mediated cell spreading required the sequential activation of the Src tyrosine kinase Lyn and PI3K.…”

Section: Intracellular Signalingsupporting

confidence: 53%

Scavenger Receptor-A (CD204): A Two-Edged Sword in Health and Disease

et al. 2014

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Scavenger receptor A (SR-A), also known as the macrophage scavenger receptor and cluster of differentiation 204 (CD204), plays roles in lipid metabolism, atherogenesis, and a number of metabolic processes. However, recent evidence points to important roles for SR-A in inflammation, innate immunity, host defense, sepsis, and ischemic injury. Herein, we review the role of SR-A in inflammation, innate immunity, host defense, sepsis, cardiac and cerebral ischemic injury, Alzheimer’s disease, virus recognition and uptake, bone metabolism, and pulmonary injury. Interestingly, SR-A is reported to be host protective in some disease states, but there is also compelling evidence that SR-A plays a role in the pathophysiology of other diseases. These observations of both harmful and beneficial effects of SR-A are discussed here in the framework of inflammation, innate immunity, and endoplasmic reticulum stress.

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“…These results are, to our knowledge, the first demonstration of an interaction (direct or indirect) between SR-A and a RTK. A variety of previous studies [75,76,84,85] has provided indirect evidence that SR-A associates with tyrosine kinases, based in most cases on inhibitor studies and use of (A) Coimmunoprecipitation of PMø following AC exposure. PMø from 129P3/J mice (upper gel) or SR-AϪ/Ϫ mice (lower gel) were exposed to fivefold excess of AC for various times as indicated.…”

Section: Discussionmentioning

confidence: 99%

The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages

Todt¹,

Hu²,

Curtis

2008

Journal of Leukocyte Biology

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Apoptotic cells (AC) must be cleared by macrophages (Mø) to resolve inflammation effectively. Mertk and scavenger receptor A (SR-A) are two of many receptors involved in AC clearance. As SR-A lacks enzymatic activity or evident intracellular signaling motifs, yet seems to signal in some cell types, we hypothesized that SR-A signals via Mer receptor tyrosine kinase (Mertk), which contains a multisubstrate docking site. We induced apoptosis in murine thymocytes by dexamethasone and used Western blotting and immunoprecipitation to analyze the interaction of Mertk and SR-A in the J774A.1 (J774) murine Mø cell line and in peritoneal Mø of wild-type mice and SR-A-/- mice. Phagocytosis (but not adhesion) of AC by J774 was inhibited by anti-SR-A or function-blocking SR-A ligands. In resting J774, SR-A was associated minimally with unphosphorylated (monomeric) Mertk; exposure to AC induced a time-dependent increase in association of SR-A with Mertk in a direct or indirect manner. Anti-SR-A inhibited AC-induced phosphorylation of Mertk and of phospholipase Cgamma2, essential steps in AC ingestion. Relative to tissue Mø of wild-type mice, AC-induced Mertk phosphorylation was reduced and delayed in tissue Mø of SR-A-/- mice, as was in vitro AC ingestion at early time-points. Thus, during AC uptake by murine Mø, SR-A is essential for optimal phosphorylation of Mertk and subsequent signaling required for AC ingestion. These data support the Mertk/SR-A complex as a potential target to manipulate AC clearance and hence, resolution of inflammation and infections.

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Class A scavenger receptor-mediated cell adhesion requires the sequential activation of Lyn and PI3-kinase

Cited by 38 publications

References 32 publications

CD47 on experimentally senescent murine RBCs inhibits phagocytosis following Fcγ receptor–mediated but not scavenger receptor–mediated recognition by macrophages

CD47 on experimentally senescent murine RBCs inhibits phagocytosis following Fcγ receptor–mediated but not scavenger receptor–mediated recognition by macrophages

Scavenger Receptor-A (CD204): A Two-Edged Sword in Health and Disease

The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages

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