Effects of inhaled low molecular weight heparin on airway allergic inflammation in aerosol-ovalbumin-sensitized guinea pigs.
Low molecular weigh, heparin (LMWH) possesses multiple nonanticoagulant properties. In the present study, we observed its anti-airway allergic inflammatory effects by bronchoalveolar lavage in guinea pigs. Guinea pigs were sensitized by repeatedly inhaling aerosolized ovalbumin. LMWH (400 u/l, 800 u/l), dexamethasone (1.2 mg/1) or vehicle (normal saline) was inhaled for 7 days. Then the animals were sacrificed under anesthesia and then lavaged with ice-cold Hank's buffer immediately; bronchoalveolar lavage fluid (BALF) was prepared 24 h after the animals were challenged by antigen exposure. The effects of LMWH on total cell counts, absolute eosinophil counts and cell catalogues in BALF were studied; effects on the activity of eosinophil peroxidase (EPO) and the contents of histamine and eosinophil cationic protein (ECP) in BALF supernatant were detected. Our results showed that compared with the vehicle group, LMWH at 400 u/l and 800 u/1 could significantly reduce total cell counts, absolute eosinophil counts and percentage of eosinophils in BALF (P<0.05 and P<0.01, respectively); LMWH at 800 u/l markedly inhibited the activity of EPO in BALF supernatant (P<0.05); LMWH at 400 u/l and 800 u/l remarkably reduced the content of histamine in BALF supernatant (P<0.05 and P<0.01, respectively), LMWH at 800 u/l decreased the content of ECP (P<0.05) significantly. It suggested that LMWH exerted anti-airway allergic inflammatory action by inhibiting infiltration of inflammatory cells and reducing release of inflammatory mediators, as well as antagonizing their activities, and that LMWH could be developed as a potential anti-bronchial asthmatic drug.
Wang
Q L
QL
Department of Pharmacology, College of Pharmacy, Shandong Medical University, Jinan, PR China.
Shang
X Y
XY
Zhang
S L
SL
Ji
J B
JB
Cheng
Y N
YN
Meng
Y J
YJ
Zhu
Y J
YJ
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D001798:Blood Proteins / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D003907:Dexamethasone / Q000494:pharmacology; D047091:Eosinophil Granule Proteins; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D006168:Guinea Pigs; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism; D007958:Leukocyte Count; D010047:Ovalbumin / Q000276:immunology; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012260:Ribonucleases
D000336:Aerosols; D018926:Anti-Allergic Agents; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D006495:Heparin, Low-Molecular-Weight; D003907:Dexamethasone; D006632:Histamine; D010047:Ovalbumin; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D012260:Ribonucleases