Giant cell formation in sarcoidosis: cell fusion or proliferation with non-division?

Abstract

SummaryGranulomas are inflammatory reactions featuring macrophages, epithelioid, T and multi-nucleated giant cells (MGC). Giant cells are present in a number of granulomatous reactions, but little is known about their formation and function, especially in man. We studied MGC in the granulomatous disorder sarcoidosis. In situ labelling of lymph nodes by means of [ 3 H]-thymidine showed that proliferation and non-division of epithelioid cells leading towards giant cells was not observed in these granulomas. However, [3 H]-uridine incorporation showed MGC with labelled as well as unlabelled nuclei in the same cell, pointing to a process of fusion of epithelioid cells to form giant cells. Apoptotic bodies were incidentally found in granulomas. A novel finding was that such bodies were statistically more often found in the close vicinity of MGC, but not within these cells. These apoptotic cells appeared to be CD4 + lymphocytes or histiocytes. CD44 and CCR-5 involved in the process of fusion were expressed in MGC. In conclusion, MGC in sarcoidosis derive by cell fusion rather than by proliferation and non-division, and seem to play an active role in the induction of apoptosis in granulomas.

Biomaterial‐induced multinucleated giant cells express proinflammatory signaling molecules: A histological study in humans

“…This observation is plausible because MNGCs are formed in a proinflammatory microenvironment as a result of persistent chronic inflammation . Additionally, biomaterial‐induced MNGCs share morphological and biological properties with the pathological inflammatory giant cells observed in sarcoidosis and tuberculosis that are similarly formed in response to persistent chronic inflammation . Consequently, proinflammatory MNGCs and macrophages contribute to biomaterial degradation and enhance vascularization .…”

“…32 Additionally, biomaterial-induced MNGCs share morphological and biological properties with the pathological inflammatory giant cells observed in sarcoidosis and tuberculosis that are similarly formed in response to persistent chronic inflammation. 33,34 Consequently, proinflammatory MNGCs and macrophages contribute to biomaterial degradation and enhance vascularization. 35 The histomorphometrical results of the vascularization rate underlined this statement.…”

Macrophage and Multinucleated Giant Cell Classification

“…MGC are distinct from osteoclasts, which are associated with bone and are present in normal, noninflammatory conditions. The concept that MGC are formed by macrophages fusing together is supported by fluorescentand radio-labeling studies [71,72]. This is in contrast to the mechanism of megakaryocyte formation.…”

“…The most well-known lung conditions associated with MGC include tuberculosis infection [106] and sarcoidosis [71]. There is a growing body of studies that describe MGC formation in response to particle inhalation.…”

“…There is a growing body of studies that describe MGC formation in response to particle inhalation. MGC are frequently [129] Crohn's disease and ulcerative colitis [130] Langerhans cell histiocytosis [131] Rheumatoid disease [132] Sarcoidosis [71] Vasculitides such as giant cell arteritis [133] Endogenous materials Keratin [134] Lipids [74] and cholesterol crystals [135] Monosodium urate crystals [136] Exogenous materials Engineered nanomaterials such as silver nanowires [118] and carbon nanotubes [119] Medical implants [137] Metals such as Al [138], Be [122], Zr [139], and Co/WC alloys [140] Minerals such as asbestos [141], silica [141], and talc [142] Plant materials [143] such as cactus spines, corn starch used with medical gloves, and wood splinters Infectionbacteria Brucellosis [144] Cat-scratch disease [145] Mycobacteria infection such as leprosy [146] and tuberculosis [106] Syphilis [147] Infection -fungus African histoplasmosis [148] Aspergillosis [149] Cryptococcosis [150] Infectionparasite Filariasis such as dirofilariasis [151] and onchocerciasis [152] Leishmaniasis [153] Schistosomiasis [154] observed in response to inhalation of antigens that cause hypersensitivity pneumonitis [113,114] and inhalation of other organic materials such as mycobacteria and fungi (Table 1.2). Inhalation of inorganic particles is also known to induce MGC formation.…”