Differential monocyte/macrophage interleukin-1β production due to biomaterial topography requires the β2 integrin signaling pathway.

Abstract

Monocytes/macrophages are crucial mediators of the host response to biomaterials, and their level of activation can be directly affected by material characteristics. Previous work has demonstrated that primary human monocytes cultured on polytetrafluoroethylene materials of varying topography but identical surface chemistry are differentially affected. Monocytes/macrophages on biaxially-expanded polytetrafluoroethylene with an average intranodal distance of 4.4 μm (4.4-ePTFE) produced higher levels of the inflammatory cytokine interleukin-1 beta (IL-1β) compared with monocytes/macrophages on nonporous polytetrafluoroethylene (np-PTFE). The current study provides a mechanistic understanding of this response. Scanning electron microscopy revealed that monocytes/macrophages cultured on np-PTFE were more spread than those on 4.4-ePTFE. In addition, the actin cytoskeleton and intact β2 integrin receptors were necessary for IL-1β production by monocytes/macrophages on 4.4-ePTFE. This IL-1β production also required the transcription factor nuclear factor kappa-B, another component of the β2 integrin signaling pathway, although it may not be the primary transcription factor involved. These studies demonstrate the importance of several β2 integrin signaling components to the monocyte/macrophage response to biomaterial topography.