Cytokine induction of the ability of human monocyte CD44 to bind hyaluronan is mediated primarily by TNF-alpha and is inhibited by IL-4 and IL-13.

Journal Article (Journal Article)

Ligation of CD44 by hyaluronan (HA) is a key proinflammatory event that regulates lymphocyte and monocyte adhesion and cytokine production. While most immune cells express CD44, few immune cells constitutively bind HA. We have previously shown that monocyte CD44 acquires the ability to bind HA after in vitro culture of PBMC in human serum and, therefore, we have investigated a series of human cytokines and bacterial LPS for their ability to induce and/or inhibit monocyte CD44 to bind HA. We found that IL-1alpha, IL-1beta, IL-3, granulocyte macrophage (GM)-CSF, and TNF-alpha, as well as bacterial LPS, all directly induced peripheral blood monocytes to bind HA. In contrast, IL-2 and IL-15 up-regulated monocyte CD44 HA-binding in PBMC suspensions, but not in purified monocyte suspensions. An anti-TNF-alpha-neutralizing Ab inhibited IL-1alpha-, IL-1beta-, IL-3-, and GM-CSF-mediated monocyte HA binding. In addition, treatment of IL-2- and IL-15-stimulated PBMC cultures with an anti-TNF-alpha Ab prevented IL-2- and IL-15-induced monocyte HA binding, thus identifying TNF-alpha as a lymphocyte-derived factor that acted on monocytes to induce HA binding. In contrast, IL-4 and IL-13 were potent inhibitors of monocyte CD44-HA binding induced by either human serum or by IL-1alpha, IL-1beta, IL-3, GM-CSF, or TNF-alpha. IL-10 had dual effects on monocyte CD44-HA binding. Alone, IL-10 induced HA binding to PBMC monocyte CD44, while in contrast, IL-10 inhibited IL-1-induced monocyte CD44 binding to HA. Taken together, these studies identify a network of T cell and monocyte-derived cytokines that regulate HA binding to peripheral blood monocyte CD44, primarily through TNF-alpha.

Full Text

Duke Authors

Cited Authors

  • Levesque, MC; Haynes, BF

Published Date

  • December 15, 1997

Published In

Volume / Issue

  • 159 / 12

Start / End Page

  • 6184 - 6194

PubMed ID

  • 9550421

International Standard Serial Number (ISSN)

  • 0022-1767


  • eng

Conference Location

  • United States