Hyaluronic acid of high molecular weight inhibits proliferation and induces cell death in U937 macrophage cells

Hyaluronic acid (HA), a major glycosaminoglycan component of the extracellular matrix, has regulatory influences on cells and cellular activities. To explore the effects of a high concentration (1 mg/mL) of high molecular weight HA (500–730 kD) on U937 macrophage growth dynamics, three factors that...

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Bibliographic Details
Published in:Life sciences (1973) 2004-11, Vol.75 (26), p.3087-3102
Main Authors: Sheehan, Kyle M., DeLott, Lindsey B., West, Richard A., Bonnema, Joy D., DeHeer, David H.
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis - drug effects
Benzoxazoles
CD44
Cell Proliferation - drug effects
Extracellular Matrix Proteins - metabolism
Flow Cytometry
Fluorescent Dyes
Humans
Hyaluronan Receptors - metabolism
Hyaluronic acid
Hyaluronic Acid - pharmacology
Proliferation
Quinolinium Compounds
RHAMM
Time Factors
U937 Cells
U937 macrophages
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Summary:Hyaluronic acid (HA), a major glycosaminoglycan component of the extracellular matrix, has regulatory influences on cells and cellular activities. To explore the effects of a high concentration (1 mg/mL) of high molecular weight HA (500–730 kD) on U937 macrophage growth dynamics, three factors that influence overall cellular growth, namely proliferation, apoptosis, and cell death, were examined. Cells were cultured with HA and were analyzed by flow cytometry every 24 hours during a 168-hour period for proliferation and the presence of apoptotic and dead cells. These analyses demonstrated that HA inhibits U937 macrophage proliferation in a time-dependent manner. Through the first 72 hours, cells exhibited slowed proliferation. However, no evidence of cell division arrest or reduced cell viability was observed. Thereafter, HA continued to diminish proliferation, but induced apoptosis. This data is consistent with regulatory influences secondary to HA binding to CD44 and/or RHAMM cell surface receptors, both of which were shown to be expressed on U937 macrophages. This study demonstrates that a high concentration of high molecular weight HA greatly inhibits macrophage population growth by the dual actions of impeding cell proliferation and inducing apoptosis.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2004.02.038