Endotoxinlike Actions of Platelet-Activating Factor on Ventalitory Function and Activation of Alveolar Macrophages: Parallelism between Exercise-Induced Asthma and Effects of Endotoxin Exposures

"INTRODUCTIONPlatelet-activating factor (P AF) has been shown to mediate a broad range of biologic activities (1). Chemical analysis has shown that PAF is a glycerophospholipid with a choline polar head group, an ester-linked acyl chain at the second carbon of the glycerol backbone, and an ether linkage at the first carbon. The alkyl group attached to the first carbon can exist in a variety of chain lengths, with the C16 and C18 forms predominant in humans. The structure of P AF has been identified as 1-0-alkyl-2-acetyl-sn-glycerol-3-phosphorylcholine (2,3).PAF can be released from a variety of cell types, such as basophils, neutrophils, and alveolar macrophages ( 4-6). Stimuli for the release of P AF include calcium ionophore, phorbol esters, chemotactic agents, and zymosan. In addition, endotoxin has been shown to be a potent stimulant of P AF release from alveolar macrophages (7).P AF has been shown to have a number of pulmonary effects. It has been associated with asthma since it can cause contraction of pulmonary tissue (8) and leukotriene secretion from leukocytes (9) and induce airway constriction when inhaled by humans (10). In addition, PAF is a potent chemoattractant and can cause migration ofneutrophils into the airspaces of the lungs (11,12). Endotoxin is a lipopolysaccharide-protein complex derived from the cell walls of gram-negative bacteria. I.PS is the lipopolysaccharide portion of endotoxin. LPS contains four covalently joined subunits: lipid A, 3-deoxyoctonate, a core polysaccharide moiety, and an 0-specific antigenic polysaccharide side chain. Rough LPS contains no 0-antigen side chain. The liP.id A portion of LPS has been associated with most of the biolQgic effects of endotoxin (13). This lipid A subunit consists of a D-glucosamine disaccharide backbone substituted with four fatty acid side chains. Endotoxin is found in a wide variety of occupational settings associated with organic dusts derived from plants or animals, such as cotton, cereal grains, silage, rice, and poultry (14-18). In addition, airborne endotoxin has been found in sewage treatment plants, composting plants, offices with contaminated humidifiers, and showers or saunas (19-22)."