Could deposition of hyaluronan be an early sign of fibrotic development?

Background: In all connective tissues the major structural components are fibrous proteins and glycosaminoglycans (GAG's). One of the GAG's is hyaluronan (HYA). This is a high molecular weight polysaccharide with unique physico-chemical properties, as well as cell biological functions. The normal distribution of HYA in human bone marrow has, hitherto, not been thoroughly described. Material: Bone marrow trephine biopsies from 30 healthy adults, aged 18-60, were stained with a specific probe for HYA - HABP (Hyaluronan Binding Protein). Silver impregnation according to Laidlaw for visualization of reticulin fiber network and hematoxylin-eosin stainings were performed. In addition to the healthy adults, three patients with known bone marrow fibrosis were also studied. Results: In normal bone marrow, HYA was diffusely distributed. A more intense staining was observed around the vessels as compared with the surrounding matrix. In addition HYA was detected intracellularily in eosinophils. In the fibrotic bone marrow the HYA staining was abundant and intense. In both normal and fibrotic bone marrows the HYA staining intensity corresponded closely to the reticulin grading score. Conclusion: This study demonstrated that HYA is present in bone marrow matrix. Interestingly, eosinphils contained HYA intracellularily, probably reflecting an uptake - the reason for which is unknown. The HYA staining intensity increased with fibrotic development. As GAG synthesis precedes collagen deposition in the matrix, a progressive HYA staining intensity most likely is an early sign of fibrotic development.