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Review
. 2009 Jan;16(1):53-7.
doi: 10.1097/MOH.0b013e32831ac52e.

Giant cell formation and function

William G Brodbeck  1 , James M Anderson
Affiliations
Review

Giant cell formation and function

William G Brodbeck et al. Curr Opin Hematol. 2009 Jan.

Abstract

Purpose of review: To provide insight into the current state of understanding regarding the molecular and cellular mechanisms underlying the formation and function of various types of multinucleated giant cells.

Recent findings: Recent studies involving mainly osteoclasts and foreign body giant cells have revealed a number of common factors, for example, vitronectin, an adhesion protein, dendritic cell-specific transmembrane protein, a fusion factor, and macrophage fusion receptor, that contribute to giant cell formation and function. Insight into common molecules, receptors, and mediators of adhesion and fusion mechanisms of giant cell formation have been complicated by the wide diversity of species, models, and cell types utilized in these studies.

Summary: These recently identified factors together with the well known osteoclast receptor, alphavbeta3, may serve as potential therapeutic targets for the modulation and inhibition of multinucleated giant cell formation and function. Further studies on intracellular and intercellular signaling mechanisms modulating multinucleated giant cell formation and function are necessary for the identification of therapeutic targets as well as a better understanding of giant cell biology.

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Figures

Figure 1
Figure 1
Foreign body giant cell formation: Inflammatory and wound healing responses to implanted medical devices, prostheses, and biomaterials.
See this image and copyright information in PMC

References

    1. Helming L, Gordon S. The molecular basis of macrophage fusion. Immunobiology. 2007;219:785–793. This article reviews current knowledge of cell-to-cell fusion mediators in the development of multinucleated giant cells (MGCs). The function of MGCs during granulomatous diseases is currently unknown and there is a lack of knowledge regarding the mechanistic basis of macrophage fusion.

    1. Anderson JM, Rodriguez A, Chang DT. Foreign body reaction to biomaterials. Sem in Immunol. 2008;20:86–100. This review presents current knowledge of foreign body giant cell formation and function in the context of implanted medical devices, prostheses, and biomaterials. The importance of the chemical properties of the monocyte/macrophage adhesion substrate in the fusion of macrophages to form foreign body giant cells is identified.

    1. Lay G, Poquet Y, Salek-Peyron P, Puissegur MP, et al. Langhans giant cells from M tuberculosis-induced human granulomas cannot mediate mycobacterial uptake. J Pathol. 2007;211:76–85. This study presents a new in vitro human model of tuberculous granulomas and the role of mycobacterium virulence in modulating the phagocytosis capability of MGCs. Mycobacterium tuberculosis (high virulence) induces the differentiation of granuloma macrophages into very large MGCs that are unable to mediate bacterial uptake (phagocytosis).

    1. Puissegur MP, Lay G, Gilleron M, et al. Mycobacterial lipomannan induces granuloma macrophage fusion via a TLR2-dependent, ADAM9-and beta1 integrin-mediated pathway. J Immunol. 2007;1:3161–3169. This study, utilizing the in vitro human model of mycobacterial granulomas, delineates the role of mycobacterial envelope glycolipids in inducing MGC formation.

    1. Werner M. Giant cell tumor of bone: morphological, biological, and histogenetical aspects. International Orthopaedics. 2006;30:484–489. - PMC - PubMed

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