Journal article
Lung endothelial cell platelet-activating factor production and inflammatory cell adherence are increased in response to cigarette smoke component exposure
American journal of physiology. Lung cellular and molecular physiology, Vol.302(1), pp.L47-L55
01/01/2012
DOI: 10.1152/ajplung.00179.2011
PMCID: PMC3349370
PMID: 21984569
Abstract
An early event in the pathogenesis of emphysema is the development of inflammation associated with accumulation of polymorphonuclear leukocytes (PMN) in small airways, and inflammatory cell recruitment from the circulation involves migration across endothelial and epithelial cell barriers. Platelet-activating factor (PAF) promotes transendothelial migration in several vascular beds, and we postulated that increased PAF production in the airways of smokers might enhance inflammatory cell recruitment and exacerbate inflammation. To examine this possibility, we incubated human lung microvascular endothelial cells (HMVEC-L) with cigarette smoke extract (CSE) and found that CSE inhibits PAF-acetylhydrolase (PAF-AH) activity. This enhances HMVEC-L PAF production and PMN adherence, and adherence is blocked by PAF receptor antagonists (CV3988 or ginkgolide B). CSE also inhibited PAF-AH activity of lung endothelial cells isolated from wild-type (WT) and iPLA
2
β knockout mice, and with WT cells, CSE enhanced PAF production and RAW 264.7 cell adherence. In contrast, CSE did not affect PAF production or RAW 264.7 cell adherence to iPLA
2
β-null cells, suggesting that iPLA
2
β plays an important role in PAF production by lung endothelial cells. These findings suggest that inhibition of PAF-AH by components of cigarette smoke may initiate or exacerbate inflammatory lung disease by enhancing PAF production and promoting accumulation of inflammatory cells in small airways. In addition, iPLA
2
β is identified as a potential target for therapeutic interventions to reduce airway inflammation and the progression of chronic lung disease.
Details
- Title: Subtitle
- Lung endothelial cell platelet-activating factor production and inflammatory cell adherence are increased in response to cigarette smoke component exposure
- Creators
- Janhavi Sharma - Department of Pathology, Saint Louis University School of Medicine, St. Louis; andDawn M Young - Department of Pathology, Saint Louis University School of Medicine, St. Louis; andJohn O Marentette - Department of Pathology, Saint Louis University School of Medicine, St. Louis; andPrerna Rastogi - Department of Pathology, Saint Louis University School of Medicine, St. Louis; andJohn Turk - Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MissouriJane McHowat - Department of Pathology, Saint Louis University School of Medicine, St. Louis; and
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.302(1), pp.L47-L55
- DOI
- 10.1152/ajplung.00179.2011
- PMID
- 21984569
- PMCID
- PMC3349370
- NLM abbreviation
- Am J Physiol Lung Cell Mol Physiol
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Publisher
- American Physiological Society; Bethesda, MD
- Grant note
- R37 DK34388; P41 RR00954; P60 DK20579; P30 DK56341 / National Institutes of Health
- Language
- English
- Date published
- 01/01/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984046818802771
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