35.9. FLCs as bioactive molecules in inflammatory diseases

Chapter 35

Although frequently regarded as merely a by-product of immunoglobulin synthesis (Chapter 3), there have now been a number of reports indicating a bioactive role for soluble FLCs, distinct from the pathological roles of depositing and plaque-forming FLCs (Figure 35.16). While this is still a relatively new area of inquiry, reports have been published by several independent research groups.

Van der Heijden et al. [829] and Thio et al. [828] reviewed relevant publications and, based upon their own studies of FLC-induced mast cell activation, proposed that FLCs could be an appropriate target for therapy of inflammatory diseases. This idea was explored further by Thio et al. [830], who concluded that FLCs mediated antigen-specific cellular activation and that FLC cross-linking was required to initiate a local allergic response (Section 35.7). A brief report by Hutchinson et al. [831] presented data indicating FLC binding to a number of different cell types, including lymphocytes and monocytes. Cohen and Horl [832] reviewed their research on the interaction of FLCs with neutrophils (which reduced migration, glucose uptake and apoptosis), and postulated that FLCs might interfere with the normal resolution of inflammation and contribute to the chronic inflammatory state found in patients with renal impairment. Also in the field of renal medicine, Wang and Sanders [833] and Basnayake et al. [834] published details of experiments demonstrating the generation of H2O2 following endocytosis of FLCs by renal, proximal tubular cells and the subsequent activation of the signal transduction molecule c-Src. In their experiments, monoclonal FLCs were used to challenge the cultured cells but the results might well be relevant to the raised polyclonal FLC concentrations observed in patients with CKD.