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The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts.

ABSTRACT: Foreign body multinucleated giant cells (FBGCs) and osteoclasts share several characteristics, like a common myeloid precursor cell, multinuclearity, expression of tartrate-resistant acid phosphatase (TRAcP) and dendritic cell-specific transmembrane protein (DC-STAMP). However, there is an important difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form only under pathological conditions or at the surface of foreign materials, like medical implants. Despite similarities, an important distinction between these cell types is that osteoclasts can resorb bone, but it is unknown whether FBGCs are capable of such an activity. To investigate this, we differentiated FBGCs and osteoclasts in vitro from their common CD14+ monocyte precursor cells, using different sets of cytokines. Both cell types were cultured on bovine bone slices and analyzed for typical osteoclast features, such as bone resorption, presence of actin rings, formation of a ruffled border, and characteristic gene expression over time. Additionally, both cell types were cultured on a biomimetic hydroxyapatite coating to discriminate between bone resorption and mineral dissolution independent of organic matrix proteolysis. Both cell types differentiated into multinucleated cells on bone, but FBGCs were larger and had a higher number of nuclei compared to osteoclasts. FBGCs were not able to resorb bone, yet they were able to dissolve the mineral fraction of bone at the surface. Remarkably, FBGCs also expressed actin rings, podosome belts and sealing zones--cytoskeletal organization that is considered to be osteoclast-specific. However, they did not form a ruffled border. At the gene expression level, FBGCs and osteoclasts expressed similar levels of mRNAs that are associated with the dissolution of mineral (e.g., anion exchange protein 2 (AE2), carbonic anhydrase 2 (CAII), chloride channel 7 (CIC7), and vacuolar-type H+-ATPase (v-ATPase)), in contrast the matrix degrading enzyme cathepsin K, which was hardly expressed by FBGCs. Functionally, the latter cells were able to dissolve a biomimetic hydroxyapatite coating in vitro, which was blocked by inhibiting v-ATPase enzyme activity. These results show that FBGCs have the capacity to dissolve the mineral phase of bone, similar to osteoclasts. However, they are not able to digest the matrix fraction of bone, likely due to the lack of a ruffled border and cathepsin K.

SUBMITTER: ten Harkel B

PROVIDER: S-EPMC4591016 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts.

ten Harkel Bas B Schoenmaker Ton T Picavet Daisy I DI Davison Noel L NL de Vries Teun J TJ Everts Vincent V

PloS one 20151001 10

Foreign body multinucleated giant cells (FBGCs) and osteoclasts share several characteristics, like a common myeloid precursor cell, multinuclearity, expression of tartrate-resistant acid phosphatase (TRAcP) and dendritic cell-specific transmembrane protein (DC-STAMP). However, there is an important difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form only under pathological conditions or at the surface of foreign materials, like medical implants. Despite similaritie ...[more]

PMID: 26426806

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Project description:All biomaterials, when implanted in vivo, elicit cellular and tissue responses. These responses include the inflammatory and wound healing responses, foreign body reactions, and fibrous encapsulation of the implanted materials. Macrophages are myeloid immune cells that are tactically situated throughout the tissues, where they ingest and degrade dead cells and foreign materials in addition to orchestrating inflammatory processes. Macrophages and their fused morphologic variants, the multinucleated giant cells, which include the foreign body giant cells (FBGCs) are the dominant early responders to biomaterial implantation and remain at biomaterial-tissue interfaces for the lifetime of the device. An essential aspect of macrophage function in the body is to mediate degradation of bio-resorbable materials including bone through extracellular degradation and phagocytosis. Biomaterial surface properties play a crucial role in modulating the foreign body reaction in the first couple of weeks following implantation. The foreign body reaction may impact biocompatibility of implantation devices and may considerably impact short- and long-term success in tissue engineering and regenerative medicine, necessitating a clear understanding of the foreign body reaction to different implantation materials. The focus of this review article is on the interactions of macrophages and foreign body giant cells with biomaterial surfaces, and the physical, chemical and morphological characteristics of biomaterial surfaces that play a role in regulating the foreign body response. Events in the foreign body response include protein adsorption, adhesion of monocytes/macrophages, fusion to form FBGCs, and the consequent modification of the biomaterial surface. The effect of physico-chemical cues on macrophages is not well known and there is a complex interplay between biomaterial properties and those that result from interactions with the local environment. By having a better understanding of the role of macrophages in the tissue healing processes, especially in events that follow biomaterial implantation, we can design novel biomaterials-based tissue-engineered constructs that elicit a favorable immune response upon implantation and perform for their intended applications.

Project description:The clinical manifestations of foreign body (FB) aspiration can range from an asymptomatic presentation to a life-threatening emergency. Patients may present with acute onset cough, chest pain, breathlessness or sub-acutely with unexplained hemoptysis, non-resolving pneumonia and at times, as an incidental finding on imaging. Patients with iatrogenic FB such as an aspirated broken tooth during difficult intubation or a broken instrument are more common scenarios in the intensive care unit (ICU). Patients with post-obstructive pneumonia with or without sepsis, or variable degree of hemoptysis often require ICU level of care and bronchoscopic interventions. Rigid bronchoscopy has traditionally been the modality of choice; however, with the innovation in instrumentation and wider availability of flexible bronchoscopes, most of the FB removal is now successfully performed using flexible bronchoscopy. Proceduralists choose instruments in accordance with their training and expertise. We describe the use of most common instruments including forceps, balloon catheters, and baskets. Role of cryoprobe and LASER in FB removal is reviewed as well. In general, larger working channel bronchoscopes are preferred; however, smaller working channel bronchoscopes may be used in situations when the patients are intubated with a smaller diameter endotracheal or tracheostomy tubes. Large size FB are removed en bloc with the grasping tool, bronchoscope, and endotracheal or tracheostomy tube, requiring preparation to safely re-establish the airway. After FB removal, bronchoscopy is re-performed to identify any residual FB, assess any injury to the airway, suction post-obstructive secretions or pus, control any active bleeding and remove granulation tissue that may be obstructing the airway. Additional interventions like balloon dilatation may be required to dislodge an impacted FB or to maintain patency of bronchial lumen. If bronchoscopic methods fail, surgery may be required for retrieval of FB in symptomatic patients or to resect suppurative or necrotizing lung process. Multidisciplinary approach involving intensivists, surgeons, and anesthesiologists is the key to optimal patient outcomes.

Dataset Information

The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts.

Publications

The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts.

Similar Datasets

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