Inflammatory cytokine production by immunological and foreign body multinucleated giant cells

Abstract

SUMMARYMultinucleated giant cells (MGC) are a common feature of granulomas. The mechanism of their formation has been studied extensively, but their function has not been completely characterized. A new method for the in vivo production of MGC was developed involving subcutaneous injection of microscopic nitrocellulose particles with adsorbed mycobacterial antigens into the footpads of sensitized BALB/c mice (immune [I]-MGC), or by nitrocellulose administration to non-sensitized mice (foreign body [FB]-MGC). The development of granulomas with a highly enriched MGC population was observed 2 weeks after the nitrocellulose injection. MGC were larger with a greater number of nuclei in I-MGC than in FB-MGC. From days 7±28 after nitrocellulose administration, the production of interleukin-1a (IL-1a) and tumour necrosis factor-a (TNF-a) was demonstrated in both MGC types by in situ reverse transcription±polymerase chain reaction (RT±PCR) and immunohistochemistry. After 2 months, the MGC had ceased production of IL-1a and TNF-a, but the expression of transforming growth factor-b (TGF-b) was very high, occurring together with extensive ®brosis. These results suggest that MGC are an active source of in¯ammatory cytokines, which can contribute to the initiation, maintenance and down-regulation of granulomatous in¯ammation induced by immunological and inert substances.

Hepatic granulomas in canine visceral leishmaniasis and clinical status

“…According to many authors, granulomas represent a successful T cell-dependent immune response (Sheffield 1990;Murray and Nathan, 1999;Hernandez-Pando et al, 2000). Granulomas typically require an antigen-specific immune response mediated by mononuclear cells, develop relatively slow and persist for extended periods, and are more likely to be provoked by intra rather than extracellular pathogens (McElrath et al, 1988).…”

Reconstrução fisiológica do ventrículo esquerdo: o conceito de máxima redução ventricular e mínima resposta inflamatória

“…Previous studies showed that bovine pericardium and Teflon are associated with predominantly mononuclear inflammatory infiltrations in the adjacent tissue and the induction of a graft-versus-host type immunological response. These formations constitute an active source of cytokines, which may start and maintain inflammatory processes induced by foreign substances in the organism [11][12][13][14][15].…”

Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans

“…However, at sites of resistant infectious agents (e.g., tuberculosis) or poorly bio-degradable tissue irritants (i.e., foreign bodies), macrophages remain activated and fuse to form multinucleate giant cells (MGCs) that can persist for weeks or months surrounding the unresolved site. At these sites, MGCs actively phagocytose debris and can acutely produce proinflammatory cytokines (interleukin-1 ␣ , TNF-␣ ) until the insult is either cleared by phagocytosis or encapsulated (12).…”