Recombinant human platelet-activating factor-acetylhydrolase inhibits airway inflammation and hyperreactivity in mouse asthma model.
Numerous in vitro and in vivo studies in both animal models and human asthmatics have implicated platelet-activating factor (PAF) as an important inflammatory mediator in asthma. In a murine asthma model, we examined the anti-inflammatory activities of recombinant human PAF-acetylhydrolase (rPAF-AH), which converts PAF to biologically inactive lyso-PAF. In this model, mice sensitized to OVA by i.p. and intranasal (i.n.) routes are challenged with the allergen by i.n. administration. The OVA challenge elicits an eosinophil infiltration into the lungs with widespread mucus occlusion of the airways and results in bronchial hyperreactivity. The administration of rPAF-AH had a marked effect on late-phase pulmonary inflammation, which included a significant reduction in airway eosinophil infiltration, mucus hypersecretion, and airway hyperreactivity in response to methacholine challenge. These studies demonstrate that elevating plasma levels of PAF-AH through the administration of rPAF-AH is effective in blocking the late-phase pulmonary inflammation that occurs in this murine allergen-challenge asthma model. These results suggest that rPAF-AH may have therapeutic effects in patients with allergic airway inflammation.
Henderson
W R
WR
Departments of Medicine and Pathology, University of Washington, Seattle, WA 98195, USA. joangb@u.washington.edu
Lu
J
J
Poole
K M
KM
Dietsch
G N
GN
Chi
E Y
EY
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001249:Asthma / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D010741:Phospholipases A / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000276:immunology; D011994:Recombinant Proteins / Q000097:blood / Q000276:immunology / Q000494:pharmacology*
D000485:Allergens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015848:Interleukin-5; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D016210:Methacholine Chloride; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase