CD44 regulates macrophage recruitment to the lung in lipopolysaccharide- induced airway disease

John W. Hollingsworth, Zhuowei Li, David M. Brass, Stavros Carantziotis, Sarah H. Timberlake, Andrew Kim, Imtaz Hossain, Rashmin C. Savani, David A. Schwartz

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

LPS from bacteria is ubiquitous in the environment and can cause airway disease and modify allergic asthma. Identification of gene products that modulate the biologic response to inhaled LPS will improve our understanding of inflammatory airways disease. Previous work has identified quantitative trait loci for the response to inhaled LPS on chromosomes 2 and 11. In these regions, 28 genes had altered RNA expression after inhalation of LPS, including CD44, which was associated with differences in both TNF-α levels and neutrophil recruitment into the lung. It has previously been shown that CD44 can modulate macrophage recruitment in response to Mycobacterium tuberculosis, as well as clearance of neutrophils after lung injury with both bleomycin and live Escherichia coli bacteria. In this study, we demonstrate that the biologic response to inhaled LPS is modified by CD44. Macrophages failed to be recruited to the lungs of CD44-deficient animals at all time points after LPS exposure. CD44-deficient macrophages showed reduced motility in a Transwell migration assay, reduced ability to secrete the proinflammatory cytokine TNF-α, reduced in vivo migration in response to monocyte chemotactic protein-1, and diminished adhesion to vascular endothelia in the presence of TNF-α. In addition, CD44-deficient animals had 150% fewer neutrophils at 24 h and 50% greater neutrophils 48 h after LPS exposure. These results support the role of CD44 in modulating the biologic response to inhaled LPS.

Original languageEnglish (US)
Pages (from-to)248-253
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume37
Issue number2
DOIs
StatePublished - Aug 1 2007

Keywords

  • Endotoxin
  • Environment
  • Hyaluronan
  • Lung
  • tlr4

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Hollingsworth, J. W., Li, Z., Brass, D. M., Carantziotis, S., Timberlake, S. H., Kim, A., Hossain, I., Savani, R. C., & Schwartz, D. A. (2007). CD44 regulates macrophage recruitment to the lung in lipopolysaccharide- induced airway disease. American journal of respiratory cell and molecular biology, 37(2), 248-253. https://doi.org/10.1165/rcmb.2006-0363OC