Authors: E M Moussa J Kotarek J S Blum E Marszal E M Topp
Publish Date: 2016/04/01
Volume: 33, Issue: 7, Pages: 1736-1751
Abstract
To investigate in vitro the innate immune response to accelerated stressinduced aggregates of intravenous immunoglobulin IGIV using a welldefined human cellline model and to correlate the innate response to physical properties of the aggregatesIGIV aggregates were prepared by applying various accelerated stress methods and particle size count and structure were characterized Immune cell activation as tracked by inflammatory cytokines released in response to aggregates was evaluated in vitro using peripheral blood mononuclear cells PBMC primary monocytes and immortalized human monocytelike cell linesIGIV aggregates produced by mechanical stress induced higher cytokine release by PBMC and primary monocytes than aggregates formed by other stresses Results with the monocytic cell line THP1 paralleled trends in PBMC and primary monocytes Effects were dosedependent enhanced by complement opsonization and partially inhibited by blocking tolllike receptors TLR2 and TLR4 and to a lesser extent by blocking Fc gamma receptors FcγRsStressinduced IGIV aggregates stimulate a dosedependent cytokine response in human monocytes and THP1 cells mediated in part by TLRs FcγRs and complement opsonization THP1 cells resemble primary monocytes in many respects with regard to tracking the innate response to IgG aggregates Accordingly the measurement of inflammatory cytokines released by THP1 cells provides a readily accessible assay system to screen for the potential innate immunogenicity of IgG aggregates The results also highlight the role of aggregate structure in interacting with the different receptors mediating innate immunity
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