Expression of platelet-activating factor receptor mRNA in human and guinea pig lung.

Abstract

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)

Platelet-Activating Factor Receptor Develops Airway Hyperresponsiveness Independently of Airway Inflammation in a Murine Asthma Model

“…Similarly to the present data, the muscarinic receptor-binding activities (B max and K d ) of the PAF receptor transgenic mice were indistinguishable from those of wild-type control mice (35). Because PAF receptor mRNA was detected in airway smooth muscle in human peripheral lung (62), it is possible for PAF to modulate the M 3 receptor-evoked smooth muscle contraction at the level of intracellular signal transduction. Whereas M 3 receptor on smooth muscle cells couples to phosphoinositol turnover through G q/11 (61), PAF receptor is capable of coupling to G i/o and G q/11 (14), suggesting a stimulatory cross talk between the intracellular signals from the two distinct receptors (63).…”

Acute severe asthma: pathophysiology and pathobiology of gas exchange abnormalities

“…Thus, microvascular leakage of plasma is an inflammatory hallmark of paramount relevance in asthma, generally referred to as abnormally increased vascular permeability. A substantially increased number of PAF receptors are reported in the lungs of asthmatic individuals [52]. Collectively, all these findings lend further support to the view that PAF may be of particular relevance to the pathogenesis of asthma.…”

Platelet Activating Factor as a Mediator and Therapeutic Approach in Bronchial Asthma

“…PAF receptor mRNA levels in peripheral blood eosinophils from atopic asthmatic patients were significantly higher than those in normal subjects [10]. Moreover, expression of PAF receptor mRNA levels was significantly increased in the lungs of asthmatic patients [11].…”