Abstract
Platelet-activating factor (PAF) is a phospholipid mediator known to produce several features of airway inflammation. We examined the effects of intravenous PAF on vascular permeability and granulocyte recruitment in the rat trachea. To assess vascular permeability, anesthetized rats were given injections of Evans blue dye (30 mg/kg, iv) and PAF (1–10µg/kg, iv), and then their tracheas were removed and assayed spectrophotometrically for dye content. We found that a PAF dosage of 6µg/kg increased the tracheal dye content 7-fold compared to controls. The amount of extravasated dye in the tracheas was significantly increased 1 min after PAF injection, was maximal at 5 min, and had returned to control levels by 10 min. To assess granulocyte recruitment, anesthetized rats were given an injection of PAF (6µg/kg, iv), and then their tracheas were removed and stained to reveal myeloperoxidase-containing neutrophils and eosinophils. We found that the number of neutrophils in the tracheal mucosa was increased 7-fold from controls 5 min after PAF injection, but was not significantly increased 6 h later. The number of eosinophils in the tracheal mucosa was not significantly increased from controls at any time after PAF injection. We conclude that intravenous PAF causes a rapid but transient increase in vascular permeability in the rat trachea, and that intravenous PAF also causes a rapid but transient recruitment of neutrophils into the tracheal mucosa without a similar effect on eosinophils.
Similar content being viewed by others
References
Arnoux B, Denjean A, Page CP, Nolibe D, Morley J, Benveniste J (1988) Accumulation of platelets and eosinophils in baboon lung after Paf-acether challenge. Am Rev Respir Dis 137:855–860
Barnes PJ (1988) Platelet-activating factor as a mediator of asthma. In: Braquet P (ed) The role of platelet-activating factor in immune disorders. New trends in lipid mediators research, vol. 2. Karger, Basel, pp 107–117
Björk J, Lindbom L, Gerdin B, Smedegård G, Arfors K-E, Benveniste J (1983) Paf-acether (platelet-activating factor) increases microvascular permeability and affects endothelium-granulocyte interaction in microvascular beds. Acta Physiol Scand 119:305–308
Brokaw JJ, Hillenbrand CM, White GW, McDonald DM (1990) Mechanism of tachyphylaxis associated with neurogenic plasma extravasation in the rat trachea. Am Rev Respir Dis 141:1434–1440
Brokaw JJ, McDonald DM (1988) Neurally mediated increase in vascular permeability in the rat trachea: onset, duration, and tachyphylaxis. Exp Lung Res 14:757–767
Chung KF (1986) Role of inflammation in the hyperreactivity of the airways in asthma. Thorax 41:657–662
Chung KF, Aizawa H, Leikauf GD, Ueki IF, Evans TW, Nadel JA (1986) Airway hyperresponsiveness induced by platelet-activating factor: role of thromboxane generation. J Pharmacol Exp Ther 236:580–584
Evans TW, Chung KF, Rogers DF, Barnes PJ (1987) Effect of platelet-activating factor on airway vascular permeability: possible mechanisms. J Appl. Physiol 63:479–484
Evans TW, Dent G, Rogers DF, Aursudkij B, Chung KF, Barnes PJ (1988) Effect of a Paf antagonist, WEB 2086, on airway microvascular leakage in the guinea-pig and platelet aggregation in man. Br J Pharmacol 94:164–168
Frigas E, Gleich GJ (1986) The eosinophil and the pathophysiology of asthma. J Allergy Clin Immunol 77:527–537
Graham RC Jr, Karnovsky MJ (1966) The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem 14:291–302
Handley DA, Arbeeny CM, Lee ML, Van Valen RG, Saunders RN (1984) Effect of platelet activating factor on endothelial permeability to plasma macromolecules. Immunopharmacology 8:137–142
Lellouch-Tubiana A, Lefort J, Pirotzky E, Vargaftig BB, Pfister A (1985) Ultrastructural evidence for extravascular platelet recruitment in the lung upon intravenous injection of platelet-activating factor (PAF-acether) to guinea-pigs. Br J Exp Pathol 66:345–355
McDonald DM (1988) Neurogenic inflammation in the rat trachea. I. Changes in venules, leucocytes and epithelial cells. J Neurocytol 17:583–603
McManus LM (1987) Acute lung injury induced by intravascular platelet activating factor. In: Winslow CM, Lee ML (eds) New horizons in platelet activating factor research. John Wiley & Sons, New York, pp 233–244
McManus LM, Deavers SI (1989) Platelet activating factor in pulmonary pathobiology. Clin Chest Med 10:107–118
McManus LM, Pinckard RN (1985) Kinetics of acetyl glyceryl ether phosphorylcholine (AGEPC)-induced acute lung alterations in the rabbit. Am J Pathol 121:55–68
Morimoto H, Fujii T, Senoh H (1989) Plasma extravasation by chemical mediators in rat skin and trachea: a role of neurogenic agents on tracheal edema formation. Jpn J Pharmacol 49:389–395
O’Donnell SR, Barnett CJK (1987) Microvascular leakage to platelet activating factor in guineapig trachea and bronchi. Eur J Pharmacol 138:385–396
Pirotzky E, Page CP, Roubin R, Pfister A, Paul W, Bonnet J, Benveniste J (1984) Paf-acetherinduced plasma exudation in rat skin is independent of platelets and neutrophils. Microcirc Endothel Lymphatics 1:107–122
Saria A, Lundberg JM (1983) Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues. J Neurosci Methods 8:41–49
Sheppard D, Scypinski L, Horn J, Gordon T, Thompson JE (1986) Granulocyte-mediated airway edema in guinea pigs. J Appl Physiol 60:1213–1220
Snyder F (1989) Biochemistry of platelet-activating factor: a unique class of biologically active phospholipids. Proc Soc Exp Biol Med 190:125–135
Wardlaw AJ, Chung KF, Moqbel R, MacDonald AJ, Hartnell A, McCusker M, Collins JV, Barnes PJ, Kay AB (1990) Effects of inhaled PAF in humans on circulating and bronchoalveolar lavage fluid neutrophils. Relationship to bronchoconstriction and changes in airway responsiveness. Am Rev Respir Dis 141:386–392
Wedmore CV, Williams TJ (1981) Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature 289:646–650
Zar JH (1984) Biostatistical analysis, 2nd ed. Prentice-Hall, Englewood Cliffs, NJ, pp 185–205
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Brokaw, J.J., Prow, D.M., Kirsch, C.M. et al. Effects of platelet-activating factor on vascular permeability and granulocyte recruitment in the rat trachea. Lung 169, 109–119 (1991). https://doi.org/10.1007/BF02714148
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02714148