Chitosan drives anti-inflammatory macrophage polarisation and pro-inflammatory dendritic cell stimulation

• Published in: European cells & materials Vol. 24; pp. 136 - 52; discussion 152-3
• Main Authors: Oliveira, Marta I, Santos, Susana G, Oliveira, Maria J, Torres, Ana L, Barbosa, Mário A
• Format: Journal Article
• Language: English
• Published: Switzerland Forum Multimedia Publishing LLC 24.07.2012
• Subjects: B7-2 Antigen - biosynthesis; B7-2 Antigen - immunology; Biocompatible Materials - pharmacology; cell activation; Cell Differentiation - drug effects; Cell Movement - drug effects; Cells, Cultured; chitosan; Chitosan - pharmacology; dendritic cell; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Flow Cytometry; Histocompatibility Antigens Class II - biosynthesis; Histocompatibility Antigens Class II - immunology; Humans; immune response; immunomodulation; inflammation; Interleukin-10 - biosynthesis; Interleukin-10 - immunology; Macrophage; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; Organ Specificity; polarisation; Transforming Growth Factor beta1 - biosynthesis; Transforming Growth Factor beta1 - immunology; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - immunology
• ISSN: 1473-2262; 1473-2262
• DOI: 10.22203/eCM.v024a10

Macrophages and dendritic cells (DC) share the same precursor and play key roles in immunity. Modulation of their behaviour to achieve an optimal host response towards an implanted device is still a challenge. Here we compare the differentiation process and polarisation of these related cell populations and show that they exhibit different responses to chitosan (Ch), with human monocyte-derived macrophages polarising towards an anti-inflammatory phenotype while their DC counterparts display pro-inflammatory features. Macrophages and DC, whose interactions with biomaterials are frequently analysed using fully differentiated cells, were cultured directly on Ch films, rather than exposed to the polymer after complete differentiation. Ch was the sole stimulating factor and activated both macrophages and DC, without leading to significant T cell proliferation. After 10 d on Ch, macrophages significantly down-regulated expression of pro-inflammatory markers, CD86 and MHCII. Production of pro-inflammatory cytokines, particularly TNF-α, decreased with time for cells cultured on Ch, while anti-inflammatory IL-10 and TGF-β1, significantly increased. Altogether, these results suggest an M2c polarisation. Also, macrophage matrix metalloproteinase activity was augmented and cell motility was stimulated by Ch. Conversely, DC significantly enhanced CD86 expression, reduced IL-10 secretion and increased TNF-α and IL-1β levels. Our findings indicate that cells with a common precursor may display different responses, when challenged by the same biomaterial. Moreover, they help to further comprehend macrophage/DC interactions with Ch and the balance between pro- and anti-inflammatory signals associated with implant biomaterials. We propose that an overall pro-inflammatory reaction may hide the expression of anti-inflammatory cytokines, likely relevant for tissue repair/regeneration.