| First Author | Longphre M | Year | 1995 |
| Journal | Am J Respir Cell Mol Biol | Volume | 13 |
| Issue | 5 | Pages | 586-94 |
| PubMed ID | 7576695 | Mgi Jnum | J:30173 |
| Mgi Id | MGI:77687 | Doi | 10.1165/ajrcmb.13.5.7576695 |
| Citation | Longphre M, et al. (1995) Susceptibility to platelet-activating factor-induced airway hyperreactivity and hyperpermeability: interstrain variation and genetic control. Am J Respir Cell Mol Biol 13(5):586-94 |
| abstractText | Platelet-activating factor (PAF) is a proinflammatory mediator known to elicit changes in airway reactivity and vascular permeability, and it may also have a role in the development and progression of acute respiratory distress syndrome and asthma. We have developed a mouse model to test the hypothesis that these traits were controlled by a single gene and were mechanistically related. We further hypothesized that there was a relationship between PAF-induced hyperreactivity and baseline reactivity to acetylcholine (ACh). Among eight inbred strains of mice that exhibited significant interstrain variation in ACh reactivity, intravenous PAF induced 16 to 278% increases in reactivity to ACh (25 micrograms/kg). PAF also elicited 95 to 307% increases in lung permeability as measured by Evans blue extravasation. Both reactivity and permeability changes induced by PAF were blocked by a PAF receptor antagonist (L-659,989). Strain distribution patterns for baseline reactivity to ACh and PAF-induced hyperreactivity and lung permeability were not significantly concordant, and suggest that the variables were not interdependent. Progeny derived from AKR/J (PAF hyperresponsive) and C3H/HeJ (PAF hyporesponsive) mice were characterized for their PAF responsiveness as determined by PAF-induced hyperreactivity and hyperpermeability. The ratios of hyperresponsive and hyporesponsive phenotypes in outcross progeny were compared to those predicted for Mendelian inheritance and assessed for relatedness by chi 2 and cosegregation analyses. Results suggested that PAF-induced hyperreactivity was controlled by a single gene, but PAF-induced hyperpermeability was controlled by a more complicated interaction of factors.(ABSTRACT TRUNCATED AT 250 WORDS) |
