Effects of Platelet Activating Factor on Various Physiological Parameters of Neutrophils, Alveolar Macrophages, and Alveolar Type II Cells

"Platelet activating factor (PAF) can be released from pneumocytes following exposure to occupational dust (Am. Rev. Respir. Dis. 135:83, 1987). In addition, PAF has been shown to induce pulmonary inflammation, edema, and bronchoconstriction (Hosp. Prac. 19, 67, 1983). This investigation reports the effects of PAF on the properties of three types of cells found in the lung. PAF (1-100, K1/2 = 2.5 pH) caused depolarization of neutrophils as well as generation of chemiluminescence and secretion of hydrogen peroxide. These responses were dependent on the presence of extracellular sodium. However, PAF did not alter oxygen consumption of neutrophils. Although PAF (10 uM) caused depolarization of alveolar macrophages, no stimulation of chemiluminestence, superoxide secretion, or oxygen consumption was observed. However, PAF (10 uM). did potentiate chemiluminescence and superoxide secretion in response to zymosan (2 mg/ml) by 55% and 36%, respectively. In addition, PAF (10-90 uM) caused aggregation of alveolar macrophages. PAF (2-10 uM) also caused depolarization of type II cells, but did not affect membrane integrity or oxygen consumption. However, PAF (10-18 PM) enhanced the activities of two distinct forms of cytochrome P-450 in type II cells and caused aggregation of type II cells at PAF doses above 18 uM. These data indicate that PAF can affect the secretory activity of pulmonary phagocytes and the ability• of type II cells to detoxify foreign compounds (Bureau of Mines Grant - G1175142).INTRODUCTIONPlatelet activating factor (PAF) is a glycerophospholipid (1-0-alkyl-2-acetylsn-glycerol-3-phosphoryl choline) which has been shown to Mediate a broad range of biological activities (1-3). Its pulmonary actions include contraction of pulmonary tissue (4), secretion of leukotrienes from leukocytes (5), airway constriction (6), pulmonary edema (7), and enhanced migration of neutrophils into the airspaces of the lungs (8,9).PAF can be released from several different cell types, such as, basophils, neutrophils and alveolar macrophages, in response to a variety of particulates or membrane stimulants which include zymosan, calcium ionophore, phorbol esters, chemotactic agents, and endotoxin (10-13). Therefore, PAP may play an important role in the development of pneumoconioses by mediating pulmonary responses of lung cells to a variety of occupational dusts. To investigate this possibility, we determined the effects of PAF on several physiological parameters of neutrophils, alveolar macrophages, and alveolar type II epithelial cells."