Decreased CD47 expression during spontaneous apoptosis targets neutrophils for phagocytosis by monocyte-derived macrophages

Lawrence, Donald W.; King, Sarah B.; Frazier, William A.; Koenig, Joyce M.

doi:10.1016/j.earlhumdev.2009.09.005

Cited by 24 publications

(24 citation statements)

References 27 publications

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“…To test this possibility, we analyzed changes in apoptotic death in neutrophils from human and murine origin, with the finding that the presence of this metalloprotease triggered an increment in their apoptosis. In this regard, previous works have described the ability of proteins containing thrombospondin type-1 repeats to interact with surface proteins such as CD36 and CD47 (30,31), that can modulate neutrophil death and clearance (32,33). Hence, it is conceivable a model in which ADAMTS-12 could participate in similar protein interactions through its thrombospondin domains.…”

Section: Discussionmentioning

confidence: 99%

ADAMTS-12 Metalloprotease Is Necessary for Normal Inflammatory Response

Moncada-Pazos

Obaya

Llamazares

et al. 2012

Journal of Biological Chemistry

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Background: ADAMTS-12 is a metalloprotease of unknown biological function. Mice deficient in Adamts12 show no obvious phenotype. Results: Adamts12-deficient mice exhibit increased inflammatory response and reduced neutrophil apoptosis. Conclusion: This protease is necessary for resolution of inflammation allowing normal neutrophil apoptosis. Significance: ADAMTS-12 has a role in inflammation, contributing to better understanding of the etiology of inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

ADAMTS-12 Metalloprotease Is Necessary for Normal Inflammatory Response

Moncada-Pazos

Obaya

Llamazares

et al. 2012

Journal of Biological Chemistry

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“…In addition, a blocking monoclonal anti-CD47 antibody enhances phagocytosis of apoptotic neutrophils (28, 29). Interestingly, in our mouse toxicity studies, administration of a blocking anti-mouse CD47 antibody led to selective depletion of neutrophils, while other hematopoietic cells were unaffected (6).…”

Section: Discussionmentioning

confidence: 99%

Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47

et al. 2010

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Under normal physiologic conditions, cellular homeostasis is partly regulated by balancing pro- and anti-phagocytic signals. CD47 is highly expressed on several human cancers including acute myeloid leukemia, non-Hodgkin lymphoma, and bladder cancer, allowing cancer cells to evade phagocytosis by the innate immune system. Blockade of CD47 with a monoclonal antibody enables phagocytosis of cancer cells and leads to in vivo tumor elimination, but leaves most normal cells unaffected. In order for target cells to be phagocytosed upon blockade of an anti-phagocytic signal, we postulate that the cells must also display a potent pro-phagocytic signal. Here we identify calreticulin as a pro-phagocytic signal highly expressed on the surface of several human cancers including acute myeloid and lymphoblastic leukemias, chronic myeloid leukemia, non-Hodgkin lymphoma (NHL), bladder cancer, glioblastoma, and ovarian cancer, but minimally expressed on most normal cells. Increased CD47 expression correlated with high calreticulin levels on cancer cells, and was necessary for protection from calreticulin-mediated phagocytosis. Phagocytosis induced by anti-CD47 antibody required the interaction of target cell calreticulin with its receptor low density lipoprotein-receptor related protein (LRP) on phagocytic cells, as blockade of the calreticulin/LRP interaction prevented anti-CD47 antibody mediated phagocytosis. Lastly, increased calreticulin expression was an adverse prognostic factor in diverse tumors including neuroblastoma, bladder cancer, and NHL. These findings identify calreticulin as the dominant pro-phagocytic signal on several human cancers, provide an explanation for the selective targeting of tumor cells by anti-CD47 antibody, and highlight the balance between pro- and anti-phagocytic signals in the immune evasion of cancer.

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“…In our original study (de Almeida et al, 2005), we had reported hyperphagocytosis of peritoneal macrophages from the B10.129Ola strain used in the current study, as compared with wild type C57BL/10SnJ, but wild type B10.129Ola macrophages were not examined. The CD47-Sirpa signaling system, however, also regulates properties of polymorphonuclear cells, such as adhesion, migration and phagocytosis, as well as macrophage-mediated clearance of apoptotic neutrophils, with robust functional consequences (Parkos et al, 1996;Liu et al, 2001;Lawrence et al, 2009;Myers et al, 2011;Zen et al, 2013;Stenberg et al, 2013Stenberg et al, , 2014Greenlee-Wacker et al, 2014). Interestingly, we have found no difference between Prnp-null and wild type neutrophils taken from B10.129Ola mice in their sensitivity to spontaneous or peroxideinduced apoptosis in vitro (Mariante et al, 2012), nor in their recruitment to the peritoneal cavity following in vivo injections of zymosan (R.M.…”

Section: Discussionmentioning

confidence: 99%

Activation and function of murine primary microglia in the absence of the prion protein

Pinheiro

Linden

Mariante

2015

Journal of Neuroimmunology

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The prion protein (PrP(C)) is predominantly expressed in the nervous and immune systems and is involved in relevant cell signaling. Microglia participate in neuroimmune interactions, and their regulatory mechanisms are critical for both health and disease. Despite recent reports with a microglial cell line, little is known about the relevance of PrP(C) in brain microglia. We investigated the role of PrP(C) in mouse primary microglia, and found no differences between wild type and Prnp-null cells in cell morphology or the expression of a microglial marker. Translocation of NF-κB to the nucleus also did not differ, nor did cytokine production. The levels of iNOS were also similar and, finally, microglia of either genotype showed no differences in either rates of phagocytosis or migration, even following activation. Thus, functional roles of PrP(C) in primary microglial cells are - if present - much more subtle than in transformed microglial cell lines.

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Decreased CD47 expression during spontaneous apoptosis targets neutrophils for phagocytosis by monocyte-derived macrophages

Cited by 24 publications

References 27 publications

ADAMTS-12 Metalloprotease Is Necessary for Normal Inflammatory Response

ADAMTS-12 Metalloprotease Is Necessary for Normal Inflammatory Response

Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47

Activation and function of murine primary microglia in the absence of the prion protein

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