Am. J. Respir. Crit. Care Med., Volume 160, Number 5, November 1999, 1734-1742

Quinolines Attenuate PAF-induced Pulmonary Pressor Responses and Edema Formation

SIGRID FALK, ROLF GÖGGEL, ULRICH HEYDASCH, FRANK BRASCH, KLAUS-MICHAEL MÜLLER, ALBRECHT WENDEL, and STEFAN UHLIG

Biochemical Pharmacology, University of Konstanz, Konstanz, Germany; Division of Pulmonary Pharmacology, Research Center Borstel, Borstel, Germany; and Institute of Pathology, Professional Associations Bergmannsheil University Hospital, Bochum, Germany

In the present study we have investigated the mechanisms of pulmonary edema caused by platelet-activating factor (PAF) in isolated rat lungs as well as in mice in vivo. In blood-free perfused and ventilated rat lungs, PAF increased lung weight by 0.59 ± 0.18 g. The cyclooxygenase inhibitor aspirin (500 µM) blocked this response by one-third, and the quinolines quinine (330 µM), quinidine (100 µM), and chloroquine (100 µM) by two-thirds. Lipoxygenase inhibition (10 µM AA861) alone or in combination with thromboxane receptor antagonism (10 µM SQ29548) had no effect on PAF-induced weight gain. In combination with aspirin, quinine or quinidine completely prevented PAF-induced weight gain and the concomitant increase of the capillary filtration coefficient (K_f,c). Pretreatment with quinine in vivo prevented not only PAF-, but also endotoxin-induced edema formation as assessed by Evans Blue extravasation. In addition, in vivo quinine prevented the endotoxin-induced release of tumor neurosis factor (TNF). Furthermore, in perfused lungs quinine reduced the PAF-induced increases in airway and vascular resistance, as well as thromboxane release. These findings demonstrate the following anti-inflammatory properties of quinolines: reduction of thromboxane and TNF formation; reduction of PAF-induced vasoconstriction and bronchoconstriction; and attenuation of PAF- and lipopolysaccharide (LPS)-induced edema formation. We conclude that the PAF- induced edema consists of two separate mechanisms, one dependent on an unknown cyclooxygenase metabolite, the other one sensitive to quinolines. Falk S, Göggel R, Heydasch U, Brasch F, Müller K-M, Wendel A, Uhlig S. Quinolines attenuate PAF-induced pulmonary pressor responses and edema formation.

This article has been cited by other articles:

				T. Miyahara, K. Hamanaka, D. S. Weber, M. Anghelescu, J. R. Frost, J. A. King, and J. C. Parker Cytosolic phospholipase A2 and arachidonic acid metabolites modulate ventilator-induced permeability increases in isolated mouse lungs J Appl Physiol, February 1, 2008; 104(2): 354 - 362. [Abstract] [Full Text] [PDF]

				R. Goggel and S. Uhlig The inositol trisphosphate pathway mediates platelet-activating-factor-induced pulmonary oedema Eur. Respir. J., May 1, 2005; 25(5): 849 - 857. [Abstract] [Full Text] [PDF]

				H Takano, K Inoue, R Yanagisawa, M Sato, A Shimada, T Morita, M Sawada, K Nakamura, C Sanbongi, and T Yoshikawa Protective role of metallothionein in acute lung injury induced by bacterial endotoxin Thorax, December 1, 2004; 59(12): 1057 - 1062. [Abstract] [Full Text] [PDF]

				C. Martin, R. Goggel, A.-R. Ressmeyer, and S. Uhlig Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L250 - L257. [Abstract] [Full Text] [PDF]

				Y. Chen, G. Davis-Gorman, R. R. Watson, and P. F. McDonagh PLATELET CD62p EXPRESSION AND MICROPARTICLE FORMATION IN MURINE ACQUIRED IMMUNE DEFICIENCY SYNDROME AND CHRONIC ETHANOL CONSUMPTION Alcohol Alcohol., January 1, 2003; 38(1): 25 - 30. [Abstract] [Full Text] [PDF]

				R. Goggel, S. Hoffman, R. Nusing, S. Narumiya, and S. Uhlig Platelet-Activating Factor-induced Pulmonary Edema Is Partly Mediated by Prostaglandin E2, E-Prostanoid 3-Receptors, and Potassium Channels Am. J. Respir. Crit. Care Med., September 1, 2002; 166(5): 657 - 662. [Abstract] [Full Text] [PDF]