Expression and role of the hyaluronan receptor RHAMM in inflammation after bleomycin injury

Aisha Zaman, Zheng Cui, Joseph P. Foley, Hengjiang Zhao, Paul C. Grimm, Horace M. DeLisser, Rashmin C. Savani

Research output: Contribution to journalArticle

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Abstract

Lung injury is associated with increased concentrations of hyaluronan (hyaluronic acid, HA). HA modifies cell behavior through interaction with cell-associated receptors such as receptor for HA-mediated motility (RHAMM, CD168). Using a function blocking anti-RHAMM antibody (R36), we investigated the expression and role of RHAMM in the inflammatory response to intratracheal bleomycin in rats, Immunostaining showed increased expression of RHAMM in macrophages 4-7 d after injury. Surface biotin labeling of cells isolated by lavage confirmed increased surface expression of a 70-kD RHAMM after lung injury, and in situ hybridization demonstrated increased RHAMM mRNA in macrophages responding to injury. Time-lapse cinemicrography demonstrated a 5-fold increase in motility of alveolar macrophages from bleomycin-treated animals that was completely blocked by R36 in vitro. Further, HA-stimulated macrophage chemotaxis was also inhibited by R36. Daily administration of R36 to injured animals resulted in a 40% decrease in macrophage accumulation 7 d after injury. Further, H&E staining of tissue sections showed that bleomycin-mediated changes in lung architecture were improved with R36 treatment. Taken together with previous results showing the inhibitory effects of HA-binding peptide on inflammation and fibrosis, we conclude that the interaction of RHAMM with HA is a critical component of the recruitment of inflammatory cells to the lung after injury.

Original languageEnglish (US)
Pages (from-to)447-454
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume33
Issue number5
DOIs
StatePublished - Nov 2005

Fingerprint

CD44 Antigens
Bleomycin
Hyaluronic Acid
Inflammation
Macrophages
Wounds and Injuries
Lung Injury
Animals
Blocking Antibodies
Therapeutic Irrigation
Alveolar Macrophages
Chemotaxis
Biotin
Cell Communication
Labeling
In Situ Hybridization
Rats
Anti-Idiotypic Antibodies
Fibrosis
Tissue

Keywords

  • Bleomycin
  • Hyaluronan
  • Inflammation
  • Lung injury
  • RHAMM

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Expression and role of the hyaluronan receptor RHAMM in inflammation after bleomycin injury. / Zaman, Aisha; Cui, Zheng; Foley, Joseph P.; Zhao, Hengjiang; Grimm, Paul C.; DeLisser, Horace M.; Savani, Rashmin C.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 33, No. 5, 11.2005, p. 447-454.

Research output: Contribution to journalArticle

Zaman, Aisha ; Cui, Zheng ; Foley, Joseph P. ; Zhao, Hengjiang ; Grimm, Paul C. ; DeLisser, Horace M. ; Savani, Rashmin C. / Expression and role of the hyaluronan receptor RHAMM in inflammation after bleomycin injury. In: American Journal of Respiratory Cell and Molecular Biology. 2005 ; Vol. 33, No. 5. pp. 447-454.
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