Heart-resident CCR2+ macrophages promote neutrophil extravasation through TLR9/MyD88/CXCL5 signaling

Li, Wenjun; Hsiao, Hsi‐Min; Higashikubo, Ryuji; Saunders, Brian T.; Bharat, Ankit; Goldstein, Daniel R.; Krupnick, Alexander S.; Gelman, Andrew E.; Lavine, Kory J.; Kreisel, Daniel

doi:10.1172/jci.insight.87315

Cited by 120 publications

(107 citation statements)

References 42 publications

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“…Total RNA was isolated using QIAGEN RNeasy Mini Kit (QIAGEN), and quantitative PCR was performed as previously described (55,56). Primer sequences for mouse Tnfa, Cxcl1, Cxcl2, Cxcl5, and Rn18s were previously described (44,57). Primer sequences for mouse Il1b were 5'-GCAACTGTTCCT-…”

Section: Quantitative Pcrmentioning

confidence: 99%

Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1β

Hsiao

Fernández

Tanaka

et al. 2018

Journal of Clinical Investigation

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Ischemia-reperfusion injury, a form of sterile inflammation, is the leading risk factor for both short-term mortality following pulmonary transplantation and chronic lung allograft dysfunction. While it is well recognized that neutrophils are critical mediators of acute lung injury, processes that guide their entry into pulmonary tissue are not well understood. Here, we found that CCR2+ classical monocytes are necessary and sufficient for mediating extravasation of neutrophils into pulmonary tissue during ischemia-reperfusion injury following hilar clamping or lung transplantation. The classical monocytes were mobilized from the host spleen, and splenectomy attenuated the recruitment of classical monocytes as well as the entry of neutrophils into injured lung tissue, which was associated with improved graft function. Neutrophil extravasation was mediated by MyD88-dependent IL-1β production by graft-infiltrating classical monocytes, which downregulated the expression of the tight junction-associated protein ZO-2 in pulmonary vascular endothelial cells. Thus, we have uncovered a crucial role for classical monocytes, mobilized from the spleen, in mediating neutrophil extravasation, with potential implications for targeting of recipient classical monocytes to ameliorate pulmonary ischemia-reperfusion injury in the clinic.

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Section: Quantitative Pcrmentioning

confidence: 99%

Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1β

Hsiao

Fernández

Tanaka

et al. 2018

Journal of Clinical Investigation

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“…Within sites of injury, resident macrophages are largely replaced by infiltrating monocyte-derived macrophages drawn to the injury site by CCL2 and CCL7, along with a population of inflammatory neutrophils peaking within 1 day after injury [62]. Resident macrophages continue to be maintained through proliferation outside the infarct [62][63][64]. Infiltrating Ly6C hi monocytes and derived macrophages become the predominant leukocyte population within the injured mouse heart between 2 and 5 days postinfarction before gradually returning to steady-state numbers [65][66][67].…”

Section: Box 2 Age-associated Metabolic Changes Influencing Macrophamentioning

confidence: 99%

Macrophage Plasticity and Function in the Eye and Heart

Wang

Koenig

Lavine

et al. 2019

Trends in Immunology

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Macrophages are important mediators of inflammation and tissue remodeling. Recent insights into the heterogeneity of macrophage subpopulations have renewed interest in their functional diversity in homeostasis and disease. In addition, their plasticity enables them to perform a variety of functions in response to changing tissue contexts, such as those imposed by aging. These qualities make macrophages particularly intriguing cells given their dichotomous role in protecting against, or accelerating, diseases of the cardiovascular system and the eye, two tissues that are particularly susceptible to the effects of aging. We review novel perspectives on macrophage biology, as informed by recent studies detailing the diversity of macrophage identity and function, as well as mechanisms influencing macrophage behavior that might offer opportunities for new therapeutic strategies. New Insights into Macrophage Lineage, Function, and Plasticity in Health and Disease Highlights Recent studies combining single-cell transcriptomics, imaging, and functional assays provide mechanistic validation of prior observations indicating that murine macrophage heterogeneity contributes to diverse roles in healthy tissue and during disease response.

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“…In particular, CCR2 + macrophages contain distinct components of the NLRP3 inflammasome and are instrumental in IL-1β release ( 2 ). On the same note, chemoattractants CXCL (C-X-C motif chemokine ligand)2 and CXCL5 produced by CCR2 + resident macrophages have been shown to specifically contribute to the initial neutrophil extravasation into the ischemic area ( 21 ). Inhibition of monocyte and monocyte-derived macrophage recruitment improves outcome after acute MI and myocardial infarction-induced heart failure.…”

Section: Origin Of Cardiac Macrophagesmentioning

confidence: 99%

Cardiomyocytes and Macrophages Discourse on the Method to Govern Cardiac Repair

Gomez

Duval

Silvestre

2018

Front. Cardiovasc. Med.

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In response to pathophysiological stress, the cardiac tissue undergoes profound remodeling process that incorporates the elimination of dying resident cells, compensatory hypertrophy of functional cardiomyocytes, growth and remodeling of the vascular compartment and formation of a fibrotic scar. Accumulating evidences indicate that cardiac remodeling is, at least in part, controlled by a complex crosstalk between cardiomyocytes and macrophages. The strategic location of abundant macrophages to the proximity of cardiomyocytes suggest that they could regulate the fate of cardiomyocytes in the injured heart. As such, macrophages appear as critical support cells for cardiomyocytes and play central roles in cardiac hypertrophy, fibrosis and remodeling. Notably, the cardiac tissue expands heterogeneous population of cardiac macrophages through local proliferation of resident macrophage as well as recruitment and differentiation of blood-derived monocytes. It has also been suggested that cardiac-resident macrophages display distinct functional properties from that of monocyte-derived macrophages in cardiac tissue. Furthermore, macrophages are an overflowing source of biological entities with non-canonical roles on cardiac conduction or cardiomyocyte proliferation by regulating action potential diffusion or cardiac cell cycle reentry. Alternatively, stressed cardiomyocytes can trigger the release of a broad repertoire of instructive signals that can regulate macrophage number, skew their phenotype and therefore direct their beneficial or deleterious actions. In this review, we highlight recent discoveries describing how the intricate dialogue between cardiomyocytes and macrophages can shape the deleterious or healing signaling mechanisms in the injured cardiac tissue.

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Heart-resident CCR2+ macrophages promote neutrophil extravasation through TLR9/MyD88/CXCL5 signaling

Cited by 120 publications

References 42 publications

Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1β

Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1β

Macrophage Plasticity and Function in the Eye and Heart

Cardiomyocytes and Macrophages Discourse on the Method to Govern Cardiac Repair

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