Differential regulation of C-C chemokines during fibroblast-monocyte interactions: adhesion vs. inflammatory cytokine pathways.

The cell-to-cell interactions during chronic inflammatory diseases likely contribute to leukocyte accumulation leading to increased pathology and organ dysfunction. In particular, there is a paucity of information relating to the maintenance of chronic fibrotic diseases. Using a lung fibroblast line and enriched monocyte populations, we have investigated the activational events which contribute to the production of two C-C chemokines, macrophage inflammatory protein-1 alpha (MIP-1alpha) and monocyte chemoattractant protein-1 (MCP-1), during fibroblast-monocyte interactions. Neither the fibroblast cell line (16lu) nor isolated monocytes alone produced significant levels of MIP-1alpha or MCP-1. However, when isolated monocytes were layered onto 16 lu fibroblast monolayers a significant increase in MIP-1alpha and MCP-1 production was observed. The use of fixed cell populations indicated that the MIP-1alpha was derived from monocytes and MCP-1 from both cell populations. To examine the molecules which were required for chemokine production during the interaction, specific antibodies were used in the co-cultures. Blocking beta3-integrin interactions significantly inhibited MIP-1alpha production. In contrast, beta-integrin interactions had no effect on the MCP-1 production, while, neutralization of TNF significantly decreased MCP-1 production during the co-culture. These data indicate that fibroblast-monocyte interactions induce chemokine production through different mechanisms and a combination of these responses may contribute to the maintenance of the mononuclear cell accumulation during disease progression

Super-resolution time-resolved imaging using computational sensor fusion

Imaging across both the full transverse spatial and temporal dimensions of a scene with high precision in all three coordinates is key to applications ranging from LIDAR to fluorescence lifetime imaging. However, compromises that sacrifice, for example, spatial resolution at the expense of temporal resolution are often required, in particular when the full 3-dimensional data cube is required in short acquisition times. We introduce a sensor fusion approach that combines data having low-spatial resolution but high temporal precision gathered with a single-photon-avalanche-diode (SPAD) array with data that has high spatial but no temporal resolution, such as that acquired with a standard CMOS camera. Our method, based on blurring the image on the SPAD array and computational sensor fusion, reconstructs time-resolved images at significantly higher spatial resolution than the SPAD input, upsampling numerical data by a factor 12×12, and demonstrating up to 4×4 upsampling of experimental data. We demonstrate the technique for both LIDAR applications and FLIM of fluorescent cancer cells. This technique paves the way to high spatial resolution SPAD imaging or, equivalently, FLIM imaging with conventional microscopes at frame rates accelerated by more than an order of magnitude

Properties and Immune Function of Cardiac Fibroblasts.

This chapter will discuss the role of cardiac fibroblasts as a target of various immunological inputs as well as an immunomodulatory hub of the heart through interaction with immune cell types and chemokine or cytokine signaling. While the purpose of this chapter is to explore the immunomodulatory properties of cardiac fibroblasts, it is important to note that cardiac fibroblasts are not a homogeneous cell type, but have a unique embryological origin and molecular identity. Specific properties of cardiac fibroblasts may influence the way they interact with the heart microenvironment to promote healthy homeostatic function or respond to pathological insults. Therefore, we will briefly discuss these aspects of cardiac fibroblast biology and then focus on their immunomodulatory role in the heart. Adv Exp Med Biol 2017; 1003:35-70