Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity

Tu, Haiyue; Ren, Haoyu; Jiang, Junjie; Shao, Changshun; Shi, Yufang; Li, Peishan

doi:10.1002/advs.202306457

Cited by 4 publications

(2 citation statements)

References 202 publications

(355 reference statements)

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“…Furthermore, a total of 289 lactylation sites were detected among 181 proteins that underwent lactylation modifications in Kupffer cells [ 38 ]. Pyroptosis is a regulated inflammatory modality of cellular demise distinguished by cellular enlargement, lysis, and the liberation of intracellular constituents [ 39 ]. Moreover, we revealed that Sal B reduced the expression of H3K18la sites and the downstream NLRP3/caspase-1/IL-1β inflammatory pathway in M1 macrophages.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages

Hu,

Yang,

et al. 2024

Molecules

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Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of Salvia miltiorrhiza Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B’s effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl4-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury.

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Section: Discussionmentioning

confidence: 99%

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages

Hu,

Yang,

et al. 2024

Molecules

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“…The lower neutrophil percentage in osteopenic, sarcopenic, and osteosarcopenic patients may be a reactive response influenced by various factors, including age. Pro-inflammatory cytokines, such as IL6 and IL1β, contribute significantly to the phenomenon of inflammation, both during sarcopenia and osteoporosis, also enhancing PGE2 [ 46 , 47 ]. PGE2, associated with osteoclastogenesis, contributes to bone resorption in osteoporosis [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

A Pilot Study on Circulating, Cellular, and Tissue Biomarkers in Osteosarcopenic Patients

Salamanna,

Faldini,

Veronesi

et al. 2024

IJMS

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Aging comes with the loss of muscle and bone mass, leading to a condition known as osteosarcopenia. Circulating, cellular, and tissue biomarkers research for osteosarcopenia is relatively scarce and, currently, no established biomarkers exist. Here we find that osteosarcopenic patients exhibited elevated basophils and TNFα levels, along with decreased aPPT, PT/INR, IL15, alpha-Klotho, DHEA-S, and FGF-2 expression and distinctive bone and muscle tissue micro-architecture and biomarker expressions. They also displayed an increase in osteoclast precursors with a concomitant imbalance towards spontaneous osteoclastogenesis. Similarities were noted with osteopenic and sarcopenic patients, including a lower neutrophil percentage and altered cytokine expression. A linear discriminant analysis (LDA) on models based on selected biomarkers showed a classification accuracy in the range of 61–78%. Collectively, our data provide compelling evidence for novel biomarkers for osteosarcopenia that may hold potential as diagnostic tools to promote healthy aging.

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Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis

Ogino,

Leite,

Guerra

et al. 2024

Journal of Clinical Investigation

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Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well. More recently, nondestructive actions of neutrophil granule proteins have been reported, such as modulation of tissue remodeling and metabolism. Here, we report a completely different mechanism by which neutrophils act nondestructively, by inserting granules directly into hepatocytes. Specifically, elastase-containing granules were transferred to hepatocytes where elastase selectively degraded intracellular calcium channels to reduce cell proliferation without cytotoxicity. In response, hepatocytes increased expression of Serpin E2 and A3, which inhibited elastase activity. Elastase insertion was seen in patient specimens of alcohol-associated hepatitis, and the relationship between elastase-mediated ITPR2 degradation and reduced cell proliferation was confirmed in mouse models. Moreover, neutrophils from patients with alcohol-associated hepatitis were more prone to degranulation and more potent in reducing calcium channel expression than neutrophils from healthy individuals. This nondestructive and reversible action on hepatocytes defines a previously unrecognized role for neutrophils in the transient regulation of epithelial calcium signaling mechanisms.

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Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity

Cited by 4 publications

References 202 publications

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages

A Pilot Study on Circulating, Cellular, and Tissue Biomarkers in Osteosarcopenic Patients

Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis

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