Sinusoidal Immunity: Macrophages at the Lymphohematopoietic Interface

Gordon, Siamon; Plüddemann, Annette; Mukhopadhyay, Subhankar

doi:10.1101/cshperspect.a016378

Cited by 34 publications

(43 citation statements)

References 72 publications

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“…In our study, we observed that the CD68 + /H‐ferritin + cells were distributed widely in the tissue, without specific colonization of the subcapsular and/or medullary sini, which are the specific resident macrophage areas in the LNs . The majority of these resident macrophages are established prenatally, and these cellular compartments self‐maintain locally independently from each other within their tissue of residence and are self‐sufficient and independent of further haematopoietic input .…”

Section: Discussionmentioning

confidence: 62%

“…The majority of these resident macrophages are established prenatally, and these cellular compartments self‐maintain locally independently from each other within their tissue of residence and are self‐sufficient and independent of further haematopoietic input . In contrast, our data suggest that the CD68 + /H‐ferritin + cells are part of the additional CD68 + macrophage pool of LN macrophages, including interfollicular cells, which migrate into the LNs after immune activation, under the influence of inflammatory stimuli, and interact with various innate and adaptive cells . Although our study does not address the origin of H‐ferritin in LN tissue, our results might allow us to speculate that during AOSD, migratory macrophages colonizing the LNs may produce and secrete ferritin, thus leading to the release of inflammatory mediators .…”

Section: Discussionmentioning

confidence: 67%

“…In contrast, MSMs recognize and transfer antigens into conspicuous phagolysosomes. Furthermore, MSMs play an important role in determining survival and clearance of short-lived early immune cells [24,[31][32][33].…”

Section: Discussionmentioning

confidence: 99%

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The CD68+/H-ferritin+ cells colonize the lymph nodes of the patients with adult onset Still's disease and are associated with increased extracellular level of H-ferritin in the same tissue: correlation with disease severity and implication for pathogenesis

Ruscitti

Ciccia

Cipriani

et al. 2015

Clinical and Experimental Immunology

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Summary In this work, we aimed to evaluate the levels of ferritin enriched in H subunits (H‐ferritin) and ferritin enriched in L subunits (L‐ferritin) and the cells expressing these two molecules in the lymph node (LN) biopsies obtained from adult‐onset Still's disease (AOSD) patients, and the possible correlation among these data and the severity of the disease. Ten patients with AOSD underwent LN biopsy. All the samples were stained by immunofluorescence. A statistical analysis was performed to estimate the possible correlation among both H‐ferritin and L‐ferritin tissue expression and the clinical picture of the disease. Furthermore, the same analysis was performed to evaluate the possible correlation among the number of CD68+/H‐ferritin+ or CD68+/L‐ferritin+ cells and the clinical picture. Immunofluorescence analysis demonstrated an increased tissue H‐ferritin expression in the LNs of AOSD patients. This increased expression correlated with the severity of the disease. An increased number of CD68 macrophages expressing H‐ferritin was observed in the LN samples of our patients. Furthermore, we observed that the number of CD68+/H‐ferritin+ cells correlated significantly with the severity of the clinical picture. Our data showed an imbalance between the levels of H‐ and L‐ferritin in LNs of AOSD patients and the evidence of an increased number of CD68+/H‐ferritin+ cells in the same organs. Furthermore, a correlation among both the tissue H‐ferritin levels and the CD68+/H‐ferritin+ cells and the clinical picture was observed.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 67%

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The CD68+/H-ferritin+ cells colonize the lymph nodes of the patients with adult onset Still's disease and are associated with increased extracellular level of H-ferritin in the same tissue: correlation with disease severity and implication for pathogenesis

Ruscitti

Ciccia

Cipriani

et al. 2015

Clinical and Experimental Immunology

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“…Within the organs, a varied collection of specialized professional phagocytes lines finely branched sinusoids and monitors the circulation. Phagocytes in liver and spleen constitute a major part of the so‐called mononuclear phagocyte network and form a lymphohematopoietic interface for interaction between the clearing organs and the blood . By effectively capturing infectious or other unwanted substances, whose persistent presence might otherwise turn problematic, phagocytes enable spleen and liver to clear the blood and fulfill important homeostatic and immune functions.…”

Section: Promoting Adaptive Immunity: a New Aspect To Immune Adherence?mentioning

confidence: 99%

Old dogs—new tricks: immunoregulatory properties of C3 and C5 cleavage fragments

Verschoor

Karsten

Broadley

et al. 2016

Immunological Reviews

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The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immunoregulatory molecules that control the activation status of cells and tissue at several levels. Likewise, C3b/iC3b is more than the opsonizing fragment that facilitates engulfment and destruction of targets by phagocytes. In the circulation, it also facilitates the transport and delivery of bacteria and immune complexes to phagocytes, through a process known as immune adherence, with consequences for adaptive immunity. Here, we will discuss non-classical immunoregulatory properties of C3 and C5 cleavage fragments. We highlight the influence of anaphylatoxins on Th2 and Th17 cell development during allergic asthma with a particular emphasis on their role in the modulation of CD11b conventional dendritic cells and monocyte-derived dendritic cells. Furthermore, we discuss the control of anaphylatoxin-mediated activation of dendritic cells and allergic effector cells by adaptive immune mechanisms that involve allergen-specific IgG1 antibodies and plasma or regulatory T cell-derived IL-10 production. Finally, we take a fresh look at immune adherence with a particular focus on the development of antibacterial cytotoxic T-cell responses.

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“… combining SCI with inflammation together with splenectomy as mobilisable pool of monocytes resides in spleen [149].…”

Section: The Source Of Inflammatory Cells Was Tested Bymentioning

confidence: 99%

Understanding heterotopic ossification after spinal cord injury

Kulina¹

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Neurological heterotopic ossification (NHO) is a frequent complication of spinal cord and traumatic brain injuries (15-25% of patients) and manifests as abnormal ossification of soft tissues near joints. NHO is very debilitating and further delays rehabilitation as it causes pain, joint deformation and ankylosis and vascular and nerve compression. In the absence of an animal model the mechanisms leading to NHO are unknown and consequently there is no preventive treatment. The only effective approach to eliminate HO is complicated and expensive surgical resection. However these surgeries are delicate and can be challenging as they are performed once the NHO are mature, often large and incapacitating entrapping large blood vessels and nerves.To elucidate NHO pathophysiology, we have developed the first animal model of NHO in genetically unmodified mice. Mice underwent a spinal cord transection (SCI); muscular inflammation was induced by intramuscular injection of cardiotoxin in limbs (IM-CTX).Formation of NHO was followed by μCT and immunohistology.SCI alone or muscular inflammation alone did not induce NHO in mice. The combination of both SCI and muscular inflammation was necessary to induce NHO. This is consistent with clinical observations as NHO incidence is higher in patients with severe trauma or concomitant infection. Abundant F4/80 + macrophages, which can provide pro-anabolic support in bone formation, were detected within the inflamed muscle and associated with areas of intramuscular bone formation (confirmed by von Kossa and collagen type 1 staining). In vivo depletion of phagocytic macrophages with clodronate-loaded liposomes prevented NHO formation whereas Zoledronate treatment exacerbated NHO. This supports our hypothesis that macrophage-mediated inflammation is a key activator of NHO following SCI. To further identify the source and type of macrophages, involved in the bone formation after SCI and test some potential treatment options different knock-out mouse models were investigated. My data suggest that local muscle residential macrophages potentially play an important role in NHO.In addition we identified several populations of muscle progenitor cells that are prone to osteogenic differentiation in vitro. These data suggest that the mesenchymal progenitors that differentiate into osteoblasts in HO following spinal cord injury are already present in healthy muscles and therefore can be derived from local muscle progenitor cells rather than being recruited from the remote site, such as bone marrow.iii Finally we investigated why SCI was necessary for NHO development. My hypothesis was that SCI causes release of systemic factors priming NHO. In support of this, I showed that NHO developed in non-paralysed inflamed front limbs of mice with SCI. Also, blood plasma from mice with SCI and IM-CTX induced osteogenic differentiation of cultured muscle mesenchymal progenitor cells (mMPC) sorted from naïve mice. This suggests that systemic factors facilitating NHO, such as substance P and G-CSF are ...

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Sinusoidal Immunity: Macrophages at the Lymphohematopoietic Interface

Cited by 34 publications

References 72 publications

The CD68+/H-ferritin+ cells colonize the lymph nodes of the patients with adult onset Still's disease and are associated with increased extracellular level of H-ferritin in the same tissue: correlation with disease severity and implication for pathogenesis

The CD68+/H-ferritin+ cells colonize the lymph nodes of the patients with adult onset Still's disease and are associated with increased extracellular level of H-ferritin in the same tissue: correlation with disease severity and implication for pathogenesis

Old dogs—new tricks: immunoregulatory properties of C3 and C5 cleavage fragments

Understanding heterotopic ossification after spinal cord injury

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