Induction of IL-12 and chemokines by hyaluronan requires adhesion-dependent priming of resident but not elicited macrophages

Jennifer Hodge-Dufour, Paul W. Noble, Maureen R. Norton, Clare Bao, Maria Wysoka, Marie D. Burdick, Robert M. Stricter, Giorgio Trinchieri, Ellen Puré

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202 Scopus citations


Components of the extracellular matrix (ECM) can regulate leukocyte activation and function at inflammatory sites. Low molecular weight fragments of the ECM glycosaminoglycan hyaluronan (LMW-HA) that accumulate in inflammation, but not the ubiquitous high molecular weight form of HA (HMW-HA), have been shown to induce cytokine and/or chemokine production by alveolar and bone-marrow derived macrophages. To determine the cellular requirements for responsiveness to HA, we compared the effects of HMW-HA and LMW-HA on resident and thioglycollate-elicited murine peritoneal macrophages. We demonstrate that treatment of elicited macrophages with LMW-HA, but not with HMW-HA, stimulated production of the chemokines RANTES and macrophage inflammatory protein-1α and -1β. Further, we demonstrate that LMW-HA induced the production of biologically active IL-12, a proinflammatory cytokine not previously known to be regulated by cell-matrix interactions. The LMW-HA-induced production of IL-12 by elicited macrophages was inhibited by an anti-CD44 mAb that blocks HA binding. In contrast to elicited macrophages, freshly explanted resident peritoneal macrophages did not respond to LMW-HA. However, preculture in vitro before stimulation led to adhesion-dependent priming for LMW-HA-induced cytokine and chemokine production by resident macrophages. These results provide further evidence of the potential importance of CD44/ LMW-HA interactions in regulating the immune response at sites of inflammation and demonstrate that the state of differen-. tiation of macrophages may determine their sensitivities to matrix components.

Original languageEnglish (US)
Pages (from-to)2492-2500
Number of pages9
JournalJournal of Immunology
Issue number5
StatePublished - 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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