title: High MW hyaluronan inhibits smoke inhalation-induced lung injury and improves survival.
abstract: OBJECTIVE
  High MW hyaluronan (HMW HA) as opposed to low MW hyaluronan (LMW HA) has been shown to have anti-inflammatory and anti-apoptotic effects. We hypothesized that treatment with HMW HA would block smoke inhalation lung injury by inhibiting smoke-induced lung inflammation and airway epithelial cell apoptosis.
  
  
  METHODS
  Anesthetized, intubated male rats were randomly allocated to either control or smoke inhalation injury groups. Rats were treated with 3-mL subcutaneous normal saline solution (sham) or LMW HA (35 kDa) or HMW HA (1600 kDa) 18 h before exposure to 15 min of cotton smoke (n = 5 each). Rats were also treated post smoke inhalation with 1600 kDa HA by intra-peritoneal injection (3 mL) or intra-tracheal nebulization (200 µL). Lung neutrophil infiltration, airway apoptosis, airway mucous plugging and lung injury were assessed 4 h after smoke inhalation injury.
  
  
  RESULTS
  Rats pretreated with 1600 kDa HA had significantly less smoke-induced neutrophil infiltration, lung oedema, airway apoptosis and mucous plugging. Pretreatment with 35 kDa HA, in contrast, increased smoke-induced neutrophil infiltration and lung injury score. Intra-tracheal administration of a single dose 1600 kDa HA, but not intra-peritoneal injection, significantly improved survival post smoke inhalation.
  
  
  CONCLUSIONS
  High MW hyaluronan (1600 kDa) may prove to be a beneficial therapy for smoke inhalation through inhibition of smoke-induced inflammation, lung oedema, airway epithelial cell apoptosis and airway mucous plugging.
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Pei-ming
authors.initials: PM
authors.lastname: Huang
authors.forename: Olga
authors.initials: O
authors.lastname: Syrkina
authors.forename: Lunyin
authors.initials: L
authors.lastname: Yu
authors.forename: Rejmon
authors.initials: R
authors.lastname: Dedaj
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
authors.forename: Aviva
authors.initials: A
authors.lastname: Shiedlin
authors.forename: Yung-yang
authors.initials: YY
authors.lastname: Liu
authors.forename: Hari
authors.initials: H
authors.lastname: Garg
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Quinn
authors.forename: Charles A
authors.initials: CA
authors.lastname: Hales
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006820:Hyaluronic Acid / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D055370:Lung Injury / Q000188:drug therapy; D008297:Male; D009093:Mucus / Q000187:drug effects / Q000276:immunology; D020556:Neutrophil Infiltration / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy; D011654:Pulmonary Edema / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015208:Smoke Inhalation Injury / Q000188:drug therapy*
chemical_list: D006820:Hyaluronic Acid