H Shirasaki, M Nishikawa, IM Adcock, JC Mak, T Sakamoto, T Shimizu and PJ Barnes
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of several inflammatory pulmonary diseases, and specific binding sites have been demonstrated in human and guinea pig lung membranes by radioligand binding experiments. Both human and guinea pig PAF receptors (PAFR) have recently been cloned. We have used molecular probes to study the gene expression of PAFR in human and animal lung and in situ hybridization to determine the distribution of PAFR mRNA in peripheral lung. Northern blot analysis of total lung RNA from human lung parenchyma, using a 1.1-kb SmaI-EcoRI fragment of human PAFR cDNA or a 0.9-kb SmaI-SmaI fragment of guinea pig PAFR cDNA, demonstrated the expression of PAFR mRNA in human lung, with a single transcript of 4 kb. There was a significant increase in PAFR mRNA in the lungs of asthmatic patients and a significant decrease in PAFR mRNA in the lungs of cigarette smokers compared with normal patients. Similarly, the expression of PAFR mRNA on guinea pig and rat lung was detected as a single transcript of 3 kb, using both guinea pig and human PAFR cDNA probes. A full-length 1.8-kb human leukocyte PAFR cDNA probe was used as the DNA template for producing 35S-labeled antisense and sense cRNA probes for use in in situ hybridization studies of human peripheral lung. These studies revealed high levels of PAFR mRNA hybridization in blood vessels, moderate levels of hybridization in alveolar walls and peripheral airway smooth muscle, but no specific signal in airway epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				K. F. van der Sluijs, L. J. R. van Elden, M. Nijhuis, R. Schuurman, S. Florquin, T. Shimizu, S. Ishii, H. M. Jansen, R. Lutter, and T. van der Poll Involvement of the platelet-activating factor receptor in host defense against Streptococcus pneumoniae during postinfluenza pneumonia Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L194 - L199. [Abstract] [Full Text] [PDF]

				S. Ishii, T. Nagase, H. Shindou, H. Takizawa, Y. Ouchi, and T. Shimizu Platelet-Activating Factor Receptor Develops Airway Hyperresponsiveness Independently of Airway Inflammation in a Murine Asthma Model J. Immunol., June 1, 2004; 172(11): 7095 - 7102. [Abstract] [Full Text] [PDF]

				T. NAGASE, S. ISHII, H. SHINDOU, Y. OUCHI, and T. SHIMIZU Airway Hyperresponsiveness in Transgenic Mice Overexpressing Platelet Activating Factor Receptor Is Mediated by an Atropine-Sensitive Pathway Am. J. Respir. Crit. Care Med., January 15, 2002; 165(2): 200 - 205. [Abstract] [Full Text] [PDF]

				N. R. HENIG, M. L. AITKEN, M. C. LIU, A. S. YU, and W. R. HENDERSON Jr. Effect of Recombinant Human Platelet-activating Factor-Acetylhydrolase on Allergen-induced Asthmatic Responses Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 523 - 527. [Abstract] [Full Text] [PDF]

				B. O. Ibe, F. C. Sander, and J. U. Raj Platelet-activating factor receptors in lamb lungs are downregulated immediately after birth Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1168 - H1176. [Abstract] [Full Text] [PDF]

				W. R. Henderson Jr., J. Lu, K. M. Poole, G. N. Dietsch, and E. Y. Chi Recombinant Human Platelet-Activating Factor- Acetylhydrolase Inhibits Airway Inflammation and Hyperreactivity in Mouse Asthma Model J. Immunol., March 15, 2000; 164(6): 3360 - 3367. [Abstract] [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]

				T. NAGASE, S. ISHII, H. KATAYAMA, Y. FUKUCHI, Y. OUCHI, and T. SHIMIZU Airway Responsiveness in Transgenic Mice Overexpressing Platelet-activating Factor Receptor . Roles of Thromboxanes and Leukotrienes Am. J. Respir. Crit. Care Med., November 1, 1997; 156(5): 1621 - 1627. [Abstract] [Full Text]