Immunologic Research

, Volume 58, Issue 2–3, pp 186–192 | Cite as

Tissue integrity signals communicated by high-molecular weight hyaluronan and the resolution of inflammation

  • S. M. Ruppert
  • T. R. Hawn
  • A. Arrigoni
  • T. N. Wight
  • P. L. BollykyEmail author


The extracellular matrix polysaccharide hyaluronan (HA) exerts size-dependent effects on leukocyte behavior. Low-molecular weight HA is abundant at sites of active tissue catabolism and promotes inflammation via effects on Toll-like receptor signaling. Conversely, high-molecular weight HA is prevalent in uninjured tissues and is anti-inflammatory. We propose that the ability of high-molecular weight but not low-molecular weight HA to cross-link CD44 functions as a novel form of pattern recognition that recognizes intact tissues and communicates “tissue integrity signals” that promote resolution of local immune responses.


Hyaluronan Danger signals DAMP Integrity signal CD44 ECM 



High-molecular weight hyaluronan


Low-molecular weight hyaluronan




Pathogen-associated molecular patterns


Damage-associated molecular patterns


Toll-like receptor


Antigen-presenting cell


Dendritic cell



This work was supported by National Institutes of Health grants T32 AI07290 (to SMR); R01 DK096087-01, R01 HL113294-01A1, and U01 AI101984 (to PLB); and HL018645 and a BIRT supplement AR037296 (to TNW). The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • S. M. Ruppert
    • 1
  • T. R. Hawn
    • 2
  • A. Arrigoni
    • 1
  • T. N. Wight
    • 3
  • P. L. Bollyky
    • 1
    Email author
  1. 1.Division of Infectious DiseasesStanford University School of MedicineStanfordUSA
  2. 2.Division of Allergy and Infectious DiseasesUniversity of Washington Medical CenterSeattleUSA
  3. 3.Matrix Biology DivisionBenaroya Research InstituteSeattleUSA

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