Initial assembly of extracellular matrix occurs within a zone immediately adjacent to the chondrocyte cell surface termed the cell-associated or periceUular matrix. Assembly within the periceUular matrix compartment requires specific cell-matrix interactions to occur, that are mediated via membrane receptors. The focus of this study is to elucidate the mechanisms of assembly and retention of th...

Histochemical staining of the epiphysial growth plate revealed that free hyaluronan (i.e. available to the staining probe) was restricted to the zone of hypertrophy, where it was located in the pericellular space between the chondrocytes and the edge of the lacunae. Furthermore, the amount of hyaluronan staining was directly proportional to the size of the lacunae. Autoradiographic analysis of ...

Neutrophil elastase is a mediator common to asthma, chronic obstructive pulmonary disease, and cystic fibrosis and thought to contribute to the pathophysiology of these diseases. Previously, we found that inhaled hyaluronan blocked elastase-induced bronchoconstriction in allergic sheep through its control of tissue kallikrein. Here, we extend those studies by determining if inhaled hyaluronan c...

OBJECTIVES Hyaluronan, a major water binding component of the extracellular matrix, is synthesised within the cytosol and exported across the plasma membrane by the ABC-transporter MRP5 in fibroblasts. Although its synthesis is vital for embryogenesis, MRP5-deficient mice are without phenotype, suggesting that another transporter had substituted for the MRP5 protein. Thus, we searched for a com...

Gliomas are highly invasive, invariably fatal intracerebral tumors. It seems that receptors for hyaluronan are required for the invasive process. Hyaluronan is a major component of the extracellular matrix in the brain, and all of the gliomas express CD44, the principal receptor for hyaluronan. To investigate the role of lysosomal hyaluronidases on tumor invasion we overexpressed hyaluronidase-...

Hyaluronan is a major component of the extracellular matrix and plays pivotal roles in inflammation and cancer. Hyaluronan oligomers are frequently found in these pathological conditions, in which they exert their effects via association with the transmembrane receptor CD44. Lipid rafts are cholesterol- and glycosphingolipid-enriched membrane microdomains that may regulate membrane receptors wh...

Hyaluronan-binding function of the CD44 molecule has not been so far detected in myeloid cells. To study pure populations of primitive myeloid cells, we investigated the hyaluronan-binding function of the CD44 molecule from three myeloid cell lines: KGla, KGI, and HL60. Both KGla and KG1 cells express the CD34 antigen characteristic of the hematopoietic stem cells and HL60 cells do not; accordi...

Hyaluronan is a simple repeating disaccharide polymer, synthesized at the cell surface by integral membrane synthases. The repeating sequence is perfectly homogeneous, and is the same in all vertebrate tissues and fluids. The polymer molecular mass is more variable. Most commonly, hyaluronan is synthesized as a high-molecular mass polymer, with an average molecular mass of approximately 1000-80...

Warren Knudson, Ph.D. Department of Biochemistry Rush University Medical Center Chicago, IL 60612 USA [email protected] Warren Knudson obtained his Ph.D. from the University of Illinois in 1981 working in the laboratory of Dr. Edward Conrad. Following postdoctoral study in Dr. Bryan Toole’s laboratory, where his interest in hyaluronan began, he joined the faculty at Rush Medical College i...

Hyaluronan, a high molecular weight, negatively charged polysaccharide, is a major constituent of the extracellular matrix. High molecular weight hyaluronan is antiangiogenic, but its degradation by hyaluronidase generates proangiogenic breakdown products. Thus, by expression of hyaluronidase, cancer cells can tilt the angiogenic balance of their microenvironment. Indeed, hyaluronidase-mediated...