CHENG-HSUN LULin, Chia-HueiChia-HueiLinKO-JEN LICHIEH-YU SHENCHENG-HAN WUYU-MIN KUOLin, Ting-SyuanTing-SyuanLinCHIA-LI YUSONG-CHOU HSIEH2022-02-092022-02-092017-100360-3997https://scholars.lib.ntu.edu.tw/handle/123456789/593955CD44 is a common leukocyte adhesion molecule expressed on the surface of various cells. Hyaluronan (HA), the natural ligand of CD44, is a simple repeated disaccharide with variable molecular mass that is widely distributed on cell surfaces and the connective tissue matrix. The binding of small molecular mass HA (SMM-HA, MW < 80 kDa) to CD44 on immune-related cells elicits cell proliferation, differentiation, and cytokine production. However, the effects and molecular basis of intermediate molecular mass HA (IMM-HA, MW ≈ 500 kDa)-CD44 interactions on polymorphonuclear neutrophil (PMN) functions have not been elucidated. We hypothesised that IMM-HA would potentiate immune functions as well as SMM-HA. In the present study, we demonstrated IMM-HA and CD44 interactions enhanced normal PMN phagocytosis and IL-8 production compared to those with LPS or anti-CD45 treatment via F-actin cytoskeleton polymerization and subsequent ERK1/2- and p38-MAPK phosphorylation. Antibody-based inhibition of CD44 did not affect PMN function; however, F-actin aggregation was induced without MAPK phosphorylation. Enhanced PMN function via IMM-HA was determined to be CD44-dependent since this effect was abolished in DMSO-induced CD44(-) PMN-like cells obtained from HL-60 cells. In conclusion, we demonstrated that IMM-HA and CD44 interactions on PMNs potently elicit F-actin cytoskeleton polymerization and p38- and ERK1/2-MAPK phosphorylation to enhance PMN function.enF-actin cytoskeleton polymerization; antibody-induced receptor commitment; common leukocyte antigen; glycosaminoglycanjournal article10.1007/s10753-017-0622-5287305112-s2.0-85025107046WOS:000409472600031https://scholars.lib.ntu.edu.tw/handle/123456789/540810