Journal of Leukocyte Biology最新文献

{"title":"The interaction of galectin-8 C-terminal domain with cell surface glycoconjugates modulates membrane elasticity to stimulate antigen uptake and presentation to CD4 T cells.","authors":"Cecilia Arahi Prato, Laura Victoria Borbolla, Leonardo Lizarraga, Oscar Campetella, María Virginia Tribulatti","doi":"10.1093/jleuko/qiae214","DOIUrl":"https://doi.org/10.1093/jleuko/qiae214","url":null,"abstract":"<p><p>Galectins constitute a family of soluble lectins with unique capacity to induce macroscale rearrangements upon interacting with cell membrane glycoconjugates. Galectin-8 (Gal-8) is acknowledged for its role in facilitating antigen uptake and processing upon engaging with cell surface glycoconjugates on antigen-presenting cells (APCs). Gal-8 consists of two covalently fused N- and C-terminal carbohydrate recognition domains (N- and C-CRD), each exhibiting distinct glycan specificity. In this study, we utilized single N- and C-CRD recombinant proteins to dissect the nature of Gal-8-glycan interactions during antigen internalization enhancement. Single C-CRD was able to replicate the effect of full-length Gal-8 (FLGal-8) on antigen internalization in BMDCs. Antigen uptake enhancement was diminished in the presence of lactose or when N-glycosylation-deficient macrophages served as APCs, underscoring the significance of glycan recognition. Measurement of the elastic modulus using Atomic Force Microscopy unveiled that FLGal-8- and C-CRD-stimulated macrophages exhibited heightened membrane stiffness compared to untreated cells, providing a plausible mechanism for their involvement in endocytosis. C-CRD proved to be as efficient as FLGal-8 in promoting antigen degradation, suggesting its implication in antigen-processing induction. Lastly, C-CRD was able to replicate FLGal-8-induced antigen presentation in the MHC-II context both in vitro and in vivo. Our findings support the notion that Gal-8 binds through its C-CRD to cell surface N-glycans, thereby altering membrane mechanical forces conducive to soluble antigen endocytosis, processing, and presentation to cognate CD4 T-cells. These findings contribute to a deeper comprehension of Gal-8 and its mechanisms of action, paving the way for the development of more efficacious immunotherapies.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and Cystic Fibrosis mice.","authors":"Hasan H Öz, Cassia L Braga, Ravindra Gudneppanavar, Caterina Di Pietro, Pamela H Huang, Ping-Xia Zhang, Diane S Krause, Marie E Egan, Thomas S Murray, Emanuela M Bruscia","doi":"10.1093/jleuko/qiae218","DOIUrl":"https://doi.org/10.1093/jleuko/qiae218","url":null,"abstract":"<p><p>Extravasation of CCR2-positive monocytes into tissue and to the site of injury is a fundamental immunological response to infections. Nevertheless, exuberant recruitment and/or activity of these monocytes and monocyte-derived macrophages can propagate tissue damage, especially in chronic inflammatory disease conditions. We have previously shown that inhibiting the recruitment of CCR2-positive monocytes ameliorates lung tissue damage caused by chronic neutrophilic inflammation in cystic fibrosis (CF) mouse models. A potential concern with targeting monocyte recruitment for therapeutic benefit in CF, however, is whether they are essential for eradicating infections such as Pseudomonas aeruginosa (PA), a pathogen that commonly colonizes and damages the lungs of patients with CF. In this study, we investigated the role of CCR2-positive monocytes in the immune response to acute pulmonary PA infection. Our data show that the altered host immune response caused by the lack of monocyte recruitment to the lungs does not impact PA lung colonization, clearance, and the severity of the infection. These results also hold up in a CF mouse background, which have a hyper-inflammatory immune response, yet exhibit reduced bactericidal activity. Thus, we lay the groundwork for future studies to investigate the use of CCR2 inhibitors as a potential therapy to ameliorate lung tissue damage in CF. This could be given alone or as an adjunct therapy with CFTR modulators that significantly improve clinical outcomes for eligible patients, but do not completely resolve the persistent infection and inflammation that drive lung tissue damage.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular Methylglyoxal Accumulation in Classically Activated Mouse Macrophages is Mediated by HIF-1α.","authors":"Daniel Prantner, Stefanie N Vogel","doi":"10.1093/jleuko/qiae215","DOIUrl":"https://doi.org/10.1093/jleuko/qiae215","url":null,"abstract":"<p><p>Approximately one million cases of sepsis in the U.S.A. occur annually. The early phase of sepsis features dramatic changes in host metabolism and inflammation. While examining the effects of metabolic pathways on inflammation, we discovered that the highly reactive glycolytic metabolite, methylglyoxal (MG), accumulates intracellularly during classical activation of macrophages. Herein, we explored the role of glycolysis and the master regulator of glycolysis, Hypoxia-Inducing Factor-1α (HIF-1α), in inflammation and MG accumulation in mouse and human macrophages. To determine how HIF-1α regulates the inflammatory response of macrophages, we correlated HIF-1α stabilization with proinflammatory gene expression and MG-adduct accumulation in WT vs HIF1a-deficient macrophages treated with LPS or LPS+IFN-γ. A nearly complete loss of HIF-1α protein expression in response to the hypoxia mimetic, cobalt chloride, confirmed the phenotype of the HIF1a-deficient macrophages. Moreover, absence of HIF-1α was also associated with decreased MG accumulation. Increasing the glucose concentration in cultured macrophages was sufficient to cause accumulation of endogenous MG-adducts which correlated with increased Tnf and Il1b expression during classical activation. Use of the MG antagonist, aminoguanidine, led to a significant decrease in Tnf and Il1b expression in both mouse macrophages and in the THP-1 human macrophage cell line. Although off-target effects cannot be ruled out, these results are consistent with the possibility that MG regulates cytokine expression in classically activated macrophages. Collectively, this work suggests that HIF-1α stabilization is upstream of MG accumulation and that targeting the activity of HIF-1α in macrophages may be therapeutic during sepsis by limiting endogenous MG accumulation.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macropinocytic cups function as signal platforms for the mTORC2-AKT pathway to modulate LPS-induced cytokine expression in macrophages.","authors":"Li Wang, Xiaowei Sun, Jianan Chen, Yanan Li, Yuxin He, Jinzi Wei, Zhongyang Shen, Sei Yoshida","doi":"10.1093/jleuko/qiae074","DOIUrl":"10.1093/jleuko/qiae074","url":null,"abstract":"<p><p>Macropinocytosis is a large-scale endocytosis process primarily observed in phagocytes as part of their cellular function to ingest antigens. Once phagocytes encounter gram-negative bacteria, the receptor proteins identify lipopolysaccharides (LPSs), which trigger radical membrane ruffles that gradually change to cup-like structures. The open area of the cups closes to generate vesicles called macropinosomes. The target bacteria are isolated by the cups and engulfed by the cells as the cups close. In addition to its ingestion function, macropinocytosis also regulates the AKT pathway in macrophages. In the current study, we report that macropinocytic cups are critical for LPS-induced AKT phosphorylation (pAKT) and cytokine expression in macrophages. High-resolution scanning electron microscope observations detailed the macropinocytic cup structures induced by LPS stimulation. Confocal microscopy revealed that AKT and the kinase molecule mTORC2 were localized in the cups. The biochemical analysis showed that macropinocytosis inhibition blocked LPS-induced pAKT. RNA sequencing, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay analyses revealed that the inhibition of macropinocytosis or the AKT pathway causes a decrease in the expression of proinflammatory cytokines interlukin-6 and interlukin-1α. Moreover, activation of the transcription factor nuclear factor κB, which regulates the cytokine expression downstream of the AKT/IκB pathway, was hindered when macropinocytosis or AKT was inhibited. These results indicate that LPS-induced macropinocytic cups function as signal platforms for the AKT pathway to regulate the cytokine expression by modulating nuclear factor κB activity in LPS-stimulated macrophages. Based on these findings, we propose that macropinocytosis may be a good therapeutic target for controlling cytokine expression.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of the antiviral factors APOBEC3A and RSAD2 upon CCL2 neutralization in primary human macrophages involves NF-κB, JAK/STAT, and gp130 signaling.","authors":"Daniela Angela Covino, Iole Farina, Laura Catapano, Silvia Sozzi, Francesca Spadaro, Serena Cecchetti, Cristina Purificato, Maria Cristina Gauzzi, Laura Fantuzzi","doi":"10.1093/jleuko/qiae123","DOIUrl":"10.1093/jleuko/qiae123","url":null,"abstract":"<p><p>The CCL2/CC chemokine receptor 2 axis plays key roles in the pathogenesis of HIV-1 infection. We previously reported that exposure of monocyte-derived macrophages to CCL2 neutralizing antibody (αCCL2 Ab) restricted HIV-1 replication at postentry steps of the viral life cycle. This effect was associated with induction of transcripts coding for innate antiviral proteins, including APOBEC3A and RSAD2. This study aimed at identifying the signaling pathways involved in induction of these factors by CCL2 blocking in monocyte-derived macrophages. Through a combination of pharmacologic inhibition, quantitative reverse transcription polymerase chain reaction, Western blotting, and confocal laser-scanning microscopy, we demonstrated that CCL2 neutralization activates the canonical NF-κB and JAK/STAT pathways, as assessed by time-dependent phosphorylation of IκB, STAT1, and STAT3 and p65 nuclear translocation. Furthermore, pharmacologic inhibition of IκB kinase and JAKs strongly reduced APOBEC3A and RSAD2 transcript accumulation elicited by αCCL2 Ab treatment. Interestingly, exposure of monocyte-derived macrophages to αCCL2 Ab resulted in induction of IL-6 family cytokines, and interference with glycoprotein 130, the common signal-transducing receptor subunit shared by these cytokines, inhibited APOBEC3A and RSAD2 upregulation triggered by CCL2 neutralization. These results provide novel insights into the signal transduction pathways underlying the activation of innate responses triggered by CCL2 neutralization in macrophages. Since this response was found to be associated with protective antiviral effects, the new findings may help design innovative therapeutic approaches targeting CCL2 to strengthen host innate immunity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The IL-21/IL-21R signaling axis regulates CD4+ T-cell responsiveness to IL-12 to promote bacterial-induced colitis.","authors":"Shahram Solaymani-Mohammadi","doi":"10.1093/jleuko/qiae069","DOIUrl":"10.1093/jleuko/qiae069","url":null,"abstract":"<p><p>IL-21/IL-21R signaling dysregulation is linked to multiple chronic intestinal inflammatory disorders in humans and animal models of human diseases. In addition to its critical requirement for the generation and development of germinal center B cells, IL-21/IL-21R signaling can also regulate the effector functions of a variety of T-cell subsets. The antibody-mediated abrogation of IL-21/IL-21R signaling led to the impaired expression of IFN-γ by mucosal CD4+ T cells from human subjects with colitis, suggesting an IL-21/IL-21R-triggered positive feedback loop of the TH1 immune response in the colon. Despite recent advances in our understanding of the mechanisms underpinning the regulation of proinflammatory immune responses by the IL-21/IL-21R signaling axis, it remains unclear how this pathway or its downstream molecules contribute to inflammation during bacterial-induced colitis. This study found that IL-21 enhances the surface expression of IL-12Rβ2, but not IL-12Rβ1, in CD4+ T cells, leading to TH1 differentiation and stability. Consistently, these findings also point to an indispensable role of the IL-12Rβ2 signaling axis in promoting proinflammatory immune responses during Citrobacter rodentium-induced colitis. Genetic deletion of the IL-12Rβ2 signaling pathway led to the attenuation of C. rodentium-induced colitis in vivo. The genetic deletion of the IL-12Rβ2 signaling pathway did not alter the host's ability to respond adequately to C. rodentium infection or the ability of Il12rb2-/- mice to express antigen-specific cytokines (IFN-γ, IL-17A). IL-21 is a pleiotropic cytokine exerting a wide range of immunomodulatory functions in multiple tissues, and its direct targeting may result in undesirable off-target consequences. These findings highlight the possibility for targeted manipulations of signaling cascades downstream of main regulators of proinflammatory responses to control invading pathogens while preserving the integrity of host immune responses. A better understanding of the novel mechanisms by which IL-21/IL-21R signaling regulates bacterial-induced colitis will provide insights into the development of new therapeutic and preventive strategies to harness IL-21/IL-21R signaling or its downstream molecules to treat infectious colitis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11408709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-specific lipoxygenase deletion amplify cardiac repair activating Treg cells in chronic heart failure.","authors":"Vasundhara Kain, Gabriel Araujo Grilo, Gunjan Upadhyay, Jerry L Nadler, Charles N Serhan, Ganesh V Halade","doi":"10.1093/jleuko/qiae113","DOIUrl":"10.1093/jleuko/qiae113","url":null,"abstract":"<p><p>Splenic leukocytes, particularly macrophage-expressed lipoxygenases, facilitate the biosynthesis of resolution mediators essential for cardiac repair. Next, we asked whether deletion of 12/15 lipoxygenase (12/15LOX) in macrophages impedes the resolution of inflammation following myocardial infarction (MI). Using 12/15flox/flox and LysMcre scheme, we generated macrophage-specific 12/15LOX (Mɸ-12/15LOX-/-) mice. Young C57BL/6J wild-type and Mɸ-12/15LOX-/- male mice were subjected to permanent coronary ligation microsurgery. Mice were monitored at day 1 (d1) to d5 (as acute heart failure [AHF]) and to d56 (chronic HF) post-MI, maintaining no MI as d0 naïve control animals. Post ligation, Mɸ-12/15LOX-/- mice showed increased survival (88% vs 56%) and limited heart dysfunction compared with wild-type. In AHF, Mɸ-12/15LOX-/- mice have increased biosynthesis of epoxyeicosatrienoic acid by 30%, with the decrease in D-series resolvins, protectin, and maresin by 70% in the infarcted heart. Overall, myeloid cell profiling from the heart and spleen indicated that Mɸ-12/15LOX-/- mice showed higher immune cells with reparative Ly6Clow macrophages during AHF. In addition, the detailed immune profiling revealed reparative macrophage phenotype (Ly6Clow) in Mɸ-12/15LOX-/- mice in a splenocardiac manner post-MI. Mɸ-12/15LOX-/- mice showed an increase in myeloid population that coordinated increase of T regulatory cells (CD4+/Foxp3+) in the spleen and injured heart at chronic HF compared with wild-type. Thus, macrophage-specific deletion of 12/15LOX directs reparative macrophage phenotype to facilitate cardiac repair. The presented study outlines the complex role of 12/15LOX in macrophage plasticity and T regulatory cell signaling that indicates that resolution mediators are viable targets to facilitate cardiac repair in HF post-MI.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoresponsive Gene 1 Facilitates TLR4-agonist-Induced Augmentation of Innate Antimicrobial Immunity.","authors":"Margaret A McBride, Katherine R Caja, Tazeen K Patil, Allison M Owen, Liming Luan, Julia K Bohannon, Antonio Hernandez, Cody L Stothers, Irina A Trenary, Mohsin Rahim, Jamey D Young, M Wade Calcutt, Victoria R Stephens, Xenia Davis, Mary A Oliver, Dan Hao, Clara Si, Malik McRae, Kenny K Nguyen, Nicholas S Davis, Jingbin Wang, Naeem K Patil, Edward R Sherwood","doi":"10.1093/jleuko/qiae198","DOIUrl":"https://doi.org/10.1093/jleuko/qiae198","url":null,"abstract":"<p><p>Treatment with the toll-like receptor (TLR) 4 agonist monophosphoryl lipid A (MPLA) conditions innate immunocytes to respond robustly to subsequent infection, a phenotype termed innate immune memory. Our published studies show that metabolic reprogramming of macrophages is a prominent feature of the memory phenotype. We undertook studies to define the functional contributions of tricarboxylic acid (TCA) cycle reprogramming to innate immune memory. We observed that priming of wild type (WT) mice with MPLA potently facilitated accumulation of the TCA cycle metabolite itaconate at sites of infection and enhanced microbial clearance. Augmentation of itaconate accumulation and microbial clearance was ablated in immuneresponsive gene 1 (Irg1) -deficient mice. We further observed that MPLA potently induces expression of Irg1 and accumulation of itaconate in macrophages. Compared to WT macrophages, the ability of Irg1-deficient macrophages to kill Pseudomonas aeruginosa was impaired. We further observed that itaconate is directly antimicrobial against P. aeruginosa at pH 5, which is characteristic of the phagolysosome, and is facilitated by reactive oxygen species. MPLA-induced augmentation of glycolysis, oxidative phosphorylation and accumulation of the TCA cycle metabolites succinate and malate was decreased in Irg1 KO macrophages compared to WT controls. RNA sequencing revealed suppressed transcription of genes associated with phagolysosome function and increased expression of genes associated with cytokine production and chemotaxis in Irg1 deficient macrophages. This study identifies a contribution of itaconate to MPLA-induced augmentation of innate antimicrobial immunity via facilitation of microbial killing as well as impact on metabolic and transcriptional adaptations.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence that keratinocyte microvesicle particles carrying platelet-activating factor mediate the widespread multiorgan damage associated with intoxicated thermal burn injury.","authors":"Rushabh P Lohade, Chad Brewer, Christine M Rapp, Karen M Henkels, Wenfeng Zhang, Anita Thyagarajan, Shikshita Singh, Pranali Manjrekar, Taskin Sabit, Ravi P Sahu, Jeffrey B Travers","doi":"10.1093/jleuko/qiae078","DOIUrl":"10.1093/jleuko/qiae078","url":null,"abstract":"<p><p>Thermal burn injuries can result in significant morbidity and mortality. The combination of ethanol intoxication with thermal burn injury results in increased morbidity through an exaggerated inflammatory response involving many organs. Recent studies have linked involvement of the lipid mediator platelet-activating factor (PAF) in the pathology associated with intoxicated thermal burn injury (ITBI). The present studies tested the roles of PAF and the elevated levels of subcellular microvesicle particles (MVP) generated in response to ITBI in the subsequent multiorgan toxicity. First, thermal burn injury of HaCaT keratinocytes preincubated with ethanol resulted in augmented MVP release, which was blocked by inhibiting the PAF-generating enzyme cytosolic phospholipase A2 and the PAF receptor (PAFR). Second, ITBI of mice resulted in increased proinflammatory cytokine production and neutrophilic inflammation in multiple organs, which were not present in mice deficient in PAFRs or the MVP-generating enzyme acid sphingomyelinase (aSMase). Moreover, the increased bacterial translocation from the gut to mesenteric lymph nodes previously reported in murine ITBI was also dependent on PAFR and aSMase. MVP released from ITBI-treated keratinocytes contained high levels of PAFR agonistic activity. Finally, use of topical aSMase inhibitor imipramine following ITBI attenuated the widespread organ inflammatory response of ITBI, suggesting a potential therapeutic for this condition. These studies provide evidence for PAF-enriched MVP generated in skin, which then act on the gut PAFR, resulting in bacterial translocation as the mechanism for the multiorgan dysfunction associated with ITBI. Inasmuch as aSMase inhibitors are widely available, these studies could result in effective treatments for ITBI.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of cathelicidins in neutrophil biology.","authors":"Grace Yoon, Rodrigo Puentes, Jacquelyn Tran, Anmol Multani, Eduardo R Cobo","doi":"10.1093/jleuko/qiae112","DOIUrl":"10.1093/jleuko/qiae112","url":null,"abstract":"<p><p>Despite their relatively short lifespan, neutrophils are tasked with counteracting pathogens through various functions, including phagocytosis, production of reactive oxygen species, neutrophil extracellular traps (NETs), and host defense peptides. Regarding the latter, small cationic cathelicidins present a conundrum in neutrophil function. Although primarily recognized as microbicides with an ability to provoke pores in microbial cell walls, the ability of cathelicidin to modulate key neutrophil functions is also of great importance, including the release of chemoattractants, cytokines, and reactive oxygen species, plus prolonging neutrophil lifespan. Cumulative evidence indicates a less recognized role of cathelicidin as an \"immunomodulator\"; however, this term is not always explicit, and its relevance in neutrophil responses during infection and inflammation is seldom discussed. This review compiles and discusses studies of how neutrophils use cathelicidin to respond to infections, while also acknowledging immunomodulatory aspects of cathelicidin through potential crosstalk between sources of the peptide.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}