Biology subjects

McClure, S. F.

Publications and source records attributed to McClure, S. F..

3 recordsLinked to original sources

bioRxiv2023

Chondro/osteoclasts and mast cells are co-villains in the joint destruction of rheumatoid arthritis

Chondro/osteoclasts and mast cells are cells of interest in the cartilage and bone destruction of joints affected by rheumatoid arthritis (RA). Both are major cellular components of the vascular synovial pannus proliferation characteristic of this disease. Chondroclasts degrade calcified cartilage and osteoclasts degrade bone tissue. Chondroclasts and osteoclasts are identical cell types and differentiate from monocyte precursors. Our studies show a close microanatomical relationship between these cells and new capillary formation (shown by the lectin Psophocarpus tetragonolobus - PTL-11) in the resorption sites of the mineralized tissues. Clast and mast cells express receptors for the lectin lPHA indicating beta1,6-acetylglucosaminal transferase V (GNTase V/MGAT5) activity providing a mechanism for neoangiogenesis. In addition to an angiogenetic function for mast cells it is probable that their products control monocyte differentiation and chondro/osteoclastogenesis.

pathology↗

bioRxiv2023

Glycoprofiling of Cartilage Matrix-Forming Tumours.

Lectin staining of benign and malignant cartilage proliferations indicates restricted glycoprofiles and significant differences. In general terms benign lesions show less cellular binding and more matrical binding than malignant lesions. This suggests that in the benign category cells are less metabolically active and the matrix more structurally stable. Chondrosarcoma cells stain with the lectin lPHA indicating increased {beta}1-6 branching linkages in complex N-linked glycans which is also a known feature of carcinoma cells. Increased angiogenesis and increased mast cell numbers are present in the connective tissue septa separating lobules of chondrosarcoma. The blood vessels stain with the lectins PTL-II and lPHA. Mast cells stain with lPHA. {beta} 1-6 linkage is initiated by the Golgi-bound glycosyltransferase GnTase V. Increased {beta}1-6 linkages are believed to enhance the metastatic potential of a malignant cell by angiogenesis. LPHA ligand is present not only in chondrosarcoma cells but also in endothelial cells and mast cells of the septa. The ligand for the lectin PTL-II is a core 1 O-linked glycans produced under the auspices of the galactosyltransferase T synthase. Production of this glycans by endothelial cells is believed to be obligatory for the formation of these cells into tubes as part of the construction of functioning blood vessels. There are, therefore, two candidate genes in chondrosarcoma worthy of further study viz those for GnTase V and T synthase. Targeted disruption of the activities of these genes has therapeutic possibilities.

pathology↗

bioRxiv2022

Study of the glycome of synovial mast cells in normal tissues, osteoarthritis and rheumatoid arthritis reveals MGAT5 activity in these and endochondral cells.

Mast cells and angiogenesis play roles in the synovium of both osteoarthritis and rheumatoid disease but precise mechanisms are unclear. In a study of the glycome of human synovial biopsies from normal, osteoarthritic and rheumatoid disease cases mast cell numbers were increased in both osteoarthritic and rheumatoid disease synovial samples (the latter more than the former). Both mast cells and endothelial cells expressed receptors for the lectin Phaseolus vulgaris leukagglutinin (lPHA). Endothelial cells only expressed receptors for Psophocarpus tetragonolobus (PTL-II). Mast cells and angiogenesis are, therefore, likely to have a common pathogenetic mechanism in osteoarthritis and rheumatoid synovitis, the difference being one of degree. lPHA receptor expression in both mast cells and endothelial cells indicates {beta}l,6N-acetylglucosaminyl (GlcNAc) - transferase V (GnTaseV/MGAT5) activity. This provides a linkage between mast cells and endothelial cell proliferation. Endothelial cells show core 1 O-glycosylation (positive PTL-II staining) which is probably necessary for the formation of competent tubular structures and for continuing vascular integrity.

pathology↗