High MW hyaluronan inhibits smoke inhalation-induced lung injury and improves survival.
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.
Huang
Pei-ming
PM
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Syrkina
Olga
O
Yu
Lunyin
L
Dedaj
Rejmon
R
Zhao
Hang
H
Shiedlin
Aviva
A
Liu
Yung-yang
YY
Garg
Hari
H
Quinn
Deborah A
DA
Hales
Charles A
CA
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*
D006820:Hyaluronic Acid