Objectives: Binding of mononuclear leukocytes to hyaluronan cable structures is a well-known pathomechanism in several chronic inflammatory diseases, but has not yet described for chronic oral inflammations. The aim of this study was to evaluate if and how binding of mononuclear leukocytes to pathologic hyaluronan cable structures can be induced in human gingival fibroblasts.
Material and methods: Experiments were performed with human gingival fibroblasts and peripheral blood mononuclear cells (PBMCs) from three healthy blood donors. Gingival fibroblasts were stimulated with (1) tunicamycin, (2) polyinosinic/polycytidylic acid (Poly:IC), and (3) lipopolysaccharides (LPS) to simulate (1) ER stress and (2) viral and (3) bacterial infections, respectively. Fibroblasts were then co-incubated with PBMCs, and the number of bound and fluorescently labeled PBMCs was assessed using a fluorescence reader and microscopy. For data analysis, a linear mixed model was used.
Results: Hyaluronan-mediated binding of PBMCs to gingival fibroblasts was increased by tunicamycin and Poly(I:C) but not by LPS. Hyaluronidase treatment and co-incubation with hyaluronan transport inhibitors reduced this binding.
Conclusions: Results suggest that hyaluronan-mediated binding of blood cells might play a role in oral inflammations. A potential superior role of viruses needs to be confirmed in further clinical studies.
Clinical relevance: The linkage between pathological hyaluronan matrices and oral infections opens up potential applications of hyaluronan transport inhibitors in the treatment of chronic oral inflammations.
Keywords: Host-pathogen interactions; Hyaluronan; Hyaluronan-cables; Innate immunity; Mononuclear leukocytes.