Resolution of Lung Inflammation by CD44

  title={Resolution of Lung Inflammation by CD44},
  author={Priit Teder and R. William Vandivier and Dianhua Jiang and Jiurong Liang and Lauren Cohn and Ellen Pur{\'e} and Peter M Henson and Paul W. Noble},
  pages={155 - 158}
Successful repair after tissue injury and inflammation requires resolution of the inflammatory response and removal of extracellular matrix breakdown products. We have examined whether the cell-surface adhesion molecule and hyaluronan receptor CD44 plays a role in resolving lung inflammation. CD44-deficient mice succumb to unremitting inflammation following noninfectious lung injury, characterized by impaired clearance of apoptotic neutrophils, persistent accumulation of hyaluronan fragments at… 

Matrix regulation of lung injury, inflammation, and repair: the role of innate immunity.

It is found that Toll-like receptors 2 and 4 (TLR2 and TLR4) are responsible for macrophage inflammatory gene expression in response to hyaluronan fragments, and they have a protective role against lung injury on alveolar epithelial cells.

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Recent work investigating the role of the innate immune response in regulating the inflammatory and fibrotic response to noninfectious lung injury has identified key roles for two cell surface receptors in regulating lung inflammation and fibrosis.

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Immunoinflammatory responses and fibrogenesis

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Requirement for CD44 in activated T cell extravasation into an inflammatory site.

The migration of Vbeta8(+) cells into the peritoneal cavity was dependent on CD44 and HA, as shown by inhibition studies, and CD44-HA interactions can target lymphocytes to specific extralymphoid effector sites.

CD44 positive macrophages take up hyaluronan during lung development.

The expression and distribution of both hyaluronan and its cell-surface receptor (CD44) during lung development in the mouse are examined, suggesting that macrophages can internalize hyAluronan during lungDevelopment and could possibly play a significant role in its removal.

CD44 regulates phagocytosis of apoptotic neutrophil granulocytes, but not apoptotic lymphocytes, by human macrophages.

It is demonstrated that phagocytosis of apoptotic neutrophils, but not apoptotic lymphocytes, by human monocyte-derived macrophages is augmented rapidly following ligation of CD44 by bivalent Abs in vitro, suggesting a novel role for CD44 in inflammation and tissue repair.

Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.

The results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages, likely that resolution of inflammation depends not only on the removal of apoptosis but on active suppression of inflammatory mediator production.

Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44.

The hypothesis that HA fragments generated during inflammation induce the expression of macrophage genes which are important in the development and maintenance of the inflammatory response is supported.

Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis.

The observations suggest that coordinated CD44, MMP-9, and TGF-beta function may provide a physiological mechanism of tissue remodeling that can be adopted by malignant cells to promote tumor growth and invasion.

CD44 activation and associated primary adhesion is inducible via T cell receptor stimulation.

It is shown here that activation of CD44 and ability to engage in rolling occurs directly through polyclonal as well as Ag-specific TCR-initiated signaling, using a superantigen, and this CD44 activation does not appear to be the result of overt changes in glycosylation.

Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development

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Cytokine regulation of human lung fibroblast hyaluronan (hyaluronic acid) production. Evidence for cytokine-regulated hyaluronan (hyaluronic acid) degradation and human lung fibroblast-derived hyaluronidase.

These studies demonstrate that rIL-1, rTNF, and rIFN-gamma have complex effects on biosynthesis and degradation which alter the quantity and molecular weight of the HA produced by lung fibroblasts and show that fibroblast HA degradation is mediated by a previously unrecognized lysosomal-type hyaluronidase whose function may be regulated by altering Fibroblast-HA binding.