title: Expression and role of the hyaluronan receptor RHAMM in inflammation after bleomycin injury.
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.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Children's Hospital of Philadelphia, PA 19104-4318, USA.
authors.forename: Aisha
authors.initials: A
authors.lastname: Zaman
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cui
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Foley
authors.forename: Hengjiang
authors.initials: H
authors.lastname: Zhao
authors.forename: Paul C
authors.initials: PC
authors.lastname: Grimm
authors.forename: Horace M
authors.initials: HM
authors.lastname: Delisser
authors.forename: Rashmin C
authors.initials: RC
authors.lastname: Savani
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001761:Bleomycin / Q000633:toxicity; D002462:Cell Membrane / Q000737:chemistry; D002633:Chemotaxis; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000032:analysis / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019138:Antibodies, Blocking; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor; D001761:Bleomycin; D006820:Hyaluronic Acid