Myeloid receptor CD36 is required for early phagocytosis of myocardial infarcts and induction of Nr4a1‐dependent mechanisms of cardiac repair

Dehn, Shirley; Thorp, Edward B.

doi:10.1096/fj.201700450r

Cited by 55 publications

(55 citation statements)

References 68 publications

(81 reference statements)

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“…3f); and a continuous increase in MERTK, a key signaling receptor induced by CD36 (Fig. 3g) 20 . We note, however, that other schemes of transitions (or their absence) between these clusters are possible, and further investigation is required to decide between them.…”

Section: Putative Transitions Between Myeloid Cell Clusters Suggest Pmentioning

confidence: 94%

“…7, 2018; After acquisition, kidney biopsy samples were placed into HypoThermosol FRS preservation solution for 10-30 minutes on ice and then transferred to a cryovial containing 1 ml of CryoStor CS10 cryopreservation medium (BioLife Solutions). The cryovial was incubated on ice for [20][21][22][23][24][25][26][27][28][29][30] min and was then placed in a Mr. Frosty freezing container (Nalgene, #5100-0001) and transferred to a -80°C freezer overnight. Cryopreserved samples were then stored in liquid nitrogen and shipped on dry ice to the central processing site, where they were stored in liquid nitrogen until processing.…”

Section: Human Kidney Tissue and Urine Acquisitionmentioning

confidence: 99%

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The immune cell landscape in kidneys of lupus nephritis patients

Arazi

Rao

Berthier

et al. 2018

Preprint

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Lupus nephritis is a potentially fatal autoimmune disease, whose current treatment is ineffective and often toxic. To gain insights into disease mechanisms, we analyzed kidney samples from lupus nephritis patients and healthy controls using single-cell RNA-seq. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid, T, NK and B cells, demonstrating both pro-inflammatory and resolving responses. We found evidence of local activation of B cells correlated with an age-associated B cell signature, and of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, pointing to potential therapeutic targets. Gene expression of immune cells in urine and kidney was highly correlated, suggesting urine may be a surrogate for kidney biopsies. Our results provide a first comprehensive view of the complex network of leukocytes active in lupus nephritis kidneys.

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Section: Putative Transitions Between Myeloid Cell Clusters Suggest Pmentioning

confidence: 94%

Section: Human Kidney Tissue and Urine Acquisitionmentioning

confidence: 99%

The immune cell landscape in kidneys of lupus nephritis patients

Arazi

Rao

Berthier

et al. 2018

Preprint

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“…Given these potential inflammation-resolving and salutary activities of macrophages, we explored whether there were master transcription regulators that determined the macrophage transcriptome after stroke. We assessed the expression of several transcriptional factors, which were previously reported [40][41][42][43] to contribute to phagocytosis-related genomic reprogramming of macrophages in peripheral organs or in vitro cell cultures. In our dataset ( Figure 5B), the expression of Nr4a1, Nr1h3, and Pparg was significantly upregulated F I G U R E 5 PPARγ and STAT6 are predicted to be master regulators of macrophage efferocytic function in the poststroke brain.…”

Section: Pparγ and Stat6 Are Predicted To Be Master Regulators Of Mmentioning

confidence: 99%

Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain

et al. 2019

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Aims Blood‐borne monocytes/macrophages infiltrate the brain in massive numbers after ischemic stroke, but their impact on poststroke brain injury and recovery remains elusive. This study examined the transcriptomic changes in monocytes/macrophages after ischemic stroke and the functional implications of these changes, particularly with regards to the contribution of these cells to the phagocytic clearance of dead/dying cells (efferocytosis) in the poststroke brain. Methods We performed whole‐genome RNA sequencing on the monocyte/macrophage population sorted from mouse brain and peripheral blood 5 days after permanent focal cerebral ischemia. In addition, the spatial and temporal profiles of macrophage efferocytosis were examined in vivo by immunohistochemistry 3‐7 days after brain ischemia. Results Robust transcriptomic changes occurred in monocytes/macrophages upon infiltrating the poststroke brain. Functional enrichment analysis revealed a transcriptome of brain macrophages that strongly favored efferocytic activity. A large number of efferocytosis‐related genes were upregulated in brain macrophages, the products of which are essential components involved in various steps of efferocytosis, such as chemotaxis, recognition of dead cells, engulfment, and processing of phagosomes. The efferocytic activity of brain macrophages were verified by immunohistochemistry, wherein Iba1‐labeled microglia/macrophages effectively cleared apoptotic neurons in the infarct during the subacute stage after brain ischemia. We also identified PPARγ and STAT6 as potential upstream regulators that shaped this proefferocytic and inflammation‐resolving transcriptome of macrophages in the poststroke brain. Conclusion Macrophages play a crucial role in the phagocytic clearance of dead neurons after ischemic stroke and promote the resolution of inflammation in the brain. Molecular therapies that enhance macrophage efferocytic capability may be promising treatments for ischemic stroke by facilitating inflammation resolution, brain repair, and recovery of neurological functions.

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“…16,17 CD36 is required for early cardiac repair through phagocytosis of dying cardiomyocytes after myocardial infarction. 18 A previous study found that degradation of CD36 sabotages the phagocytic capacity of macrophages and prolongs neutrophil inflammation, which delays cardiac healing postmyocardial infarction. 19 Additionally, CD36 has been found to promote the degradation and clearance of ectopic cellular debris during EM.…”

Section: Introductionmentioning

confidence: 99%

“…It serves as a class B scavenger receptor that is involved in multiple physiological and pathologic processes, including the clearance of oxidized low‐density lipoprotein and apoptotic neutrophils . CD36 is required for early cardiac repair through phagocytosis of dying cardiomyocytes after myocardial infarction . A previous study found that degradation of CD36 sabotages the phagocytic capacity of macrophages and prolongs neutrophil inflammation, which delays cardiac healing postmyocardial infarction .…”

Section: Introductionmentioning

confidence: 99%

Eutopic endometrium from patients with endometriosis modulates the expression of CD36 and SIRP‐α in peritoneal macrophages

Xie

et al. 2019

J of Obstet and Gynaecol

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Aim This study aimed to investigate the in vitro alterations of the expression of signal regulatory protein‐α (SIRP‐α) and CD36 in macrophages in the endometriosis condition. Methods The expression of SIRP‐α and CD36 was measured in peritoneal macrophages and peripheral blood mononuclear cells of endometriosis patients and control participants. The expressions of SIRP‐α and CD36 were measured in human acute monocytic leukemia (THP‐1) cell‐derived macrophages that were treated with interleukin‐6 (IL‐6)‐induced conditioned medium, eutopic versus normal endometrial homogenate, or lipopolysaccharide in the presence or absence of nuclear factor kappa‐B (NF‐κB) or transforming growth factor (TGF‐β) inhibitors, respectively. Results Peritoneal macrophages that were isolated from women with endometriosis exhibited an enhanced expression of SIRP‐α and a decreased expression of CD36 compared to control participants. Women with endometriosis had significantly higher levels of SIRP‐α and CD36 in peripheral circulating mononuclear cells than in control participants. SIRP‐α expression was significantly increased, whereas the CD36 expression was decreased in THP‐1 cell‐derived macrophages after treatment with eutopic endometrial homogenate. Intervention with IL‐6‐induced conditioned medium resulted in the downregulation of SIRP‐α but the upregulation of CD36 in THP‐1 cells. Incubation with the NF‐κBp50 inhibitor decreased the expression of CD36 and SIRP‐α in macrophages that were treated with normal endometrial homogenate, whereas the TGF‐β inhibitor enhanced the CD36 expression of THP‐1 cell‐derived macrophages treated with eutopic endometrial homogenate. Conclusion The eutopic endometrium could reduce the phagocytic ability of peritoneal macrophages in women with endometriosis through the modulation of SIRP‐α and CD36 expression. Inhibition of the TGF‐β signal pathway may be a potential therapeutic target for the treatment of endometriosis.

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Myeloid receptor CD36 is required for early phagocytosis of myocardial infarcts and induction of Nr4a1‐dependent mechanisms of cardiac repair

Cited by 55 publications

References 68 publications

The immune cell landscape in kidneys of lupus nephritis patients

The immune cell landscape in kidneys of lupus nephritis patients

Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain

Eutopic endometrium from patients with endometriosis modulates the expression of CD36 and SIRP‐α in peritoneal macrophages

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