Scavenger Receptors SR-AI/II and MARCO Limit Pulmonary Dendritic Cell Migration and Allergic Airway Inflammation

Arredouani, Mohamed S.; Franco, Francesca; Imrich, Amy; Fedulov, Alexey V.; Lü, Xin; Perkins, David L.; Soininen, Raija; Tryggvason, Karl; Shapiro, Steven D.; Kobzik, Lester

doi:10.4049/jimmunol.178.9.5912

Cited by 59 publications

(53 citation statements)

References 42 publications

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“…The MARCO receptor binds environmental particles, bacteria, and oxidized lipids. 33,[47][48][49] The absence of MARCO leads to an increased inflammatory response suggesting MARCO modulates the immune response. 50,51 In lung alveolar macrophages increased MARCO expression polarized lung alveolar macrophages toward a profibrotic M2 phenotype.…”

Section: Discussionmentioning

confidence: 99%

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

et al. 2016

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Telomere maintenance is a hallmark of cancer and likely to be targeted in future treatments. In glioblastoma established methods of identifying telomerase and alternative lengthening of telomeres leave a significant proportion of tumors with no defined telomere maintenance mechanism. This study investigated the composition of these tumors using RNA-Seq. Glioblastomas with an indeterminate telomere maintenance mechanism had an increased immune signature compared with alternative lengthening of telomeres and telomerase-positive tumors. Immunohistochemistry for CD163 confirmed that the majority (80%) of tumors with an indeterminate telomere maintenance mechanism had a high presence of tumor-associated macrophages. The RNA-Seq and immunostaining data separated tumors with no defined telomere maintenance mechanism into three subgroups: alternative lengthening of telomeres like tumors with a high presence of tumor-associated macrophages and telomerase like tumors with a high presence of tumor-associated macrophages. The third subgroup had no increase in tumor-associated macrophages and may represent a distinct category. The presence of tumorassociated macrophages conferred a worse prognosis with reduced patient survival times (alternative lengthening of telomeres with and without macrophages P = 0.0004, and telomerase with and without macrophages P = 0.013). The immune signatures obtained from RNA-Seq were significantly different between telomere maintenance mechanisms. Alternative lengthening of telomeres like tumors with macrophages had increased expression of interferon-induced proteins with tetratricopeptide repeats (IFIT1-3). Telomerase-positive tumors with macrophages had increased expression of macrophage receptor with collagenous structure (MARCO), CXCL12 and sushi-repeat containing protein x-linked 2 (SRPX2). Telomerase-positive tumors with macrophages were also associated with a reduced frequency of total/near total resections (44% vs 476% for all other subtypes, P = 0.014). In summary, different immune signatures are found among telomere maintenance mechanism-based subgroups in glioblastoma. The reduced extent of surgical resection of telomerase-positive tumors with macrophages suggests that some tumor-associated macrophages are more unfavorable.

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Section: Discussionmentioning

confidence: 99%

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

et al. 2016

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“…Recently, Sun and Metzger (51) reported that IFN-␥ suppresses the expression of MARCO, the class A scavenger receptor, on lung CD11c ϩ cells and the phagocytosis, thus inhibited antibacterial immunity. Although Arredouani et al (52) reported that deletion of MARCO enhances lung DC migration and Ag-induced eosinophilic inflammation, the role of MARCO in the Ag-induced immune response of wild-type mice has not been fully clarified. So, suppression of MARCO might also be involved in the IFN-␥-mediated suppression of T cell priming in this study, which should be elucidated in future.…”

Section: Figurementioning

confidence: 99%

IFN-γ Attenuates Antigen-Induced Overall Immune Response in the Airway As a Th1-Type Immune Regulatory Cytokine

Nakagome

Okunishi

Imamura

et al. 2009

The Journal of Immunology

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Allergic inflammation in the airway is generally considered a Th2-type immune response. However, recent studies demonstrated that Th1- and Th17-type immune responses also play important roles in this process. IFN-γ is a Th1-type cytokine that generally counteracts the Th2 response. Although previous studies suggest that exogenous IFN-γ suppresses allergic airway inflammation, the mechanism of suppression has not been fully clarified. In this study, we elucidated whether IFN-γ suppresses Ag-induced immune responses including the production of Th1- and Th17-type cytokines in the lung, and examined its mechanism of action. BALB/c mice were sensitized and challenged with OVA-Ag to induce airway inflammation. An IFN-γ-producing plasmid vector was delivered before systemic Ag sensitization. IFN-γ suppressed indicators of Th2-type immune responses such as airway eosinophilia, IL-5 and IL-13 production in the lung, and bronchial mucus production. Moreover, IFN-γ also suppressed the production of IL-17 and IFN-γ itself. The suppression was not mediated by inducing regulatory T cells or by inducing apoptosis in immunocytes. Instead, IFN-γ suppressed the Ag-presenting capacity and cytokine production of splenic dendritic cells and thus subsequently suppressed OVA-induced activation of CD4+ T cells. Furthermore, IFN-γ also attenuated allergic airway inflammation when delivered during the OVA challenge. Various functions of lung CD11c+ APCs and their migration to regional lymph nodes were also suppressed. These results suggest that the Th1 cytokine IFN-γ has broad immune regulatory potential through suppressing APC functions. They also suggest that delivery of IFN-γ could be an effective strategy for regulating Ag-induced immune responses in the lung.

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“…Whole mouse lungs were minced and digested in serum-free RPMI 1,640 medium supplemented with 1 mg/ml collagenase type IV (Sigma), 0.5 mg/ml DNase (DNase I from a bovine pancreas; Sigma), and 2 mg/ml collagenase/dispase (Roche, Indianapolis, IN) before filtering through a 70-mm cell strainer (BD Biosciences) (32). The resulting cell suspension was centrifuged at 1,400 rpm for 5 minutes at 48C, and leukocytes were isolated by separation on a 40-70% percoll (GE Lifesciences, Piscataway, NJ) gradient (33).…”

Section: Preparation Of Single-cell Suspensions and Immunofluorescentmentioning

confidence: 99%

High-Mobility Group Box 1 Contributes to Lethality of Endotoxemia in Heme Oxygenase-1–Deficient Mice

Takamiya

Hung

Hall

et al. 2009

Am J Respir Cell Mol Biol

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High-mobility group box 1 (HMGB1) is a nuclear protein that has been found to be a critical mediator of lethality in endotoxemia and sepsis. During the systemic inflammatory response, circulating levels of HMGB1 are increased, but in a delayed fashion compared with early inflammatory mediators. To counteract the inflammatory response of endotoxemia, a secondary anti-inflammatory response ensues in an attempt to prevent inflammation-induced tissue injury. One such cytoprotective gene that is induced during endotoxemia is heme oxygenase (HO)-1. HO-1, and its products of heme metabolism, possess anti-inflammatory and antioxidant properties to counter the damaging effects of endotoxemia. In the present study, we wanted to determine whether tissue and circulating levels of HMGB1 are increased further in the absence of HO-1 during endotoxemia, and whether this increase may contribute to the pathobiology of endotoxemia. Lung inflammation, HMGB1 protein levels, and expression of HMGB1 in inflammatory cells were increased in HO-1 2/2 mice compared with HO-1 1/1 mice. After the administration of LPS, tissue levels of HMGB1 were not increased further in HO-1 2/2 mice; however, circulating levels of HMGB1 were higher when compared with HO-1 1/1 mice. HO-1 2/2 mice treated with a carbon monoxide-releasing molecule or biliverdin showed a reduction in plasma HMGB1, which was associated with a marked improvement in survival. HO-1 2/2 mice given HMGB1-neutralizing antibody showed improvement in survival compared with control antibody. These data suggest that exaggerated circulating levels of HMGB1 contribute to endotoxin-induced mortality in the absence of HO-1.

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Scavenger Receptors SR-AI/II and MARCO Limit Pulmonary Dendritic Cell Migration and Allergic Airway Inflammation

Cited by 59 publications

References 42 publications

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

IFN-γ Attenuates Antigen-Induced Overall Immune Response in the Airway As a Th1-Type Immune Regulatory Cytokine

High-Mobility Group Box 1 Contributes to Lethality of Endotoxemia in Heme Oxygenase-1–Deficient Mice

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