Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations

Clements, Meghan; Gershenovich, Michael; Chaber, Christopher J.; Campos‐Rivera, Juanita; Du, Pan; Zhang, Mindy; Ledbetter, Steve; Żuk, Anna

doi:10.1681/asn.2014111138

Cited by 69 publications

(69 citation statements)

References 64 publications

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“…3C) were profiled, with the cell-surface antigen Ly6C further used as a surrogate to assess myeloid cell activation states (Fig. S1 shows gating (26). A small population of Ly6C low myeloid cells was present in naïve skin, likely made up of dendritic cells and other tissue-resident immune cells (27), whereas few neutrophils, Ly6C hi monocytes, or T cells were found in the uninjured hind paw (Fig.…”

Section: Resultsmentioning

confidence: 99%

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

Ghasemlou

Chiu

Julien

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

152

135

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Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund's adjuvant (CFA) as a model of adjuvant-and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G + CD11b + neutrophils and T-cell receptor (TCR) β + T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b + Ly6G − myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2 + Ly6C hi ) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b + Ly6G − myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation.pain | inflammation | cytokines | monocytes | macrophages

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Section: Resultsmentioning

confidence: 99%

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

Ghasemlou

Chiu

Julien

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

152

135

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“…The CD11b + /Ly6C high population appeared during the acute injury phase, was linked with monocyte/macrophage immune responses, and when depleted led to renoprotection (64), as reported by others (64, 65). The CD11b + /Ly6C intermediate population was present during the repair phase, had a gene signature of wound healing, and when depleted, associated with prolonged renal injury (63). The CD11b + /Ly6C low population had a profibrotic phenotype and dominated during the progressive phase.…”

Section: Pathophysiologymentioning

confidence: 99%

Acute Kidney Injury

2016

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Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD).

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“…Emerging data from human biopsies also corroborate the presence of macrophages in AKI and their persistence in progressive chronic kidney disease; we highlight our current understanding of the mechanisms by which macrophages contribute to injury and repair after AKI. Recent analysis of macrophage populations carefully isolated by differential expressions of Ly6C in CD11b + cells in the kidney injury [31, 32] confirmed that results of previous studies have shown that macrophages (predominantly CD11b + /Ly6C high cells) [30, 31] in the kidney early expressed proinflammatory genes, whereas macrophages within the kidney during the tubular repair phase (CD11b + /Ly6C intermediate cells) expressed more wound-healing markers [30]. It has been proved that decreased MIF concentration in cancer can induce macrophage polarization from proinflammatory macrophages (predominantly CD11b + /Ly6C high cells) to pro-wound healing macrophages (CD11b + /Ly6C intermediate cells) [33].…”

Section: The Role Of Crrt In Inflammation and Metabolic Adaptation Inmentioning

confidence: 99%

How Does Continuous Renal Replacement Therapy Affect Septic Acute Kidney Injury?

et al. 2018

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Sepsis is the leading cause of acute kidney injury (AKI) in the intensive care unit. As the most common treatment of septic AKI, it is believed that continuous renal replacement therapy (CRRT) can not only maintain the water balance and excrete the metabolic products but also regulate the inflammation and promote kidney recovery. CRRT can remove the inflammatory cytokines to regulate the metabolic adaption in kidney and restore the kidney recovery to protect the kidney in septic AKI. Second, CRRT can provide extra energy supply in septic AKI to improve the kidney energy balance in septic AKI. Third, the anticoagulant used in CRRT also regulates the inflammation in septic AKI. CRRT is not only a treatment to deal with the water balance and metabolic products, but also a method to regulate the inflammation in septic AKI. Video Journal Club ‘Cappuccino with Claudio Ronco’ at https://www.karger.com/Journal/ArticleNews/223997?sponsor=52.

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Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations

Cited by 69 publications

References 64 publications

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

Acute Kidney Injury

How Does Continuous Renal Replacement Therapy Affect Septic Acute Kidney Injury?

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Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations

Cited by 69 publications

References 64 publications

CD11b+Ly6G−myeloid cells mediate mechanical inflammatory pain hypersensitivity

CD11b+Ly6G−myeloid cells mediate mechanical inflammatory pain hypersensitivity

Acute Kidney Injury

How Does Continuous Renal Replacement Therapy Affect Septic Acute Kidney Injury?

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CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity