Effects of Platelet Activation Factor on Membrane Potential and Respiratory Burst Activity of Human Granulocytes

"I. INTRODUCTIONA mechanism which is present in leukocytes and capable of releasing histamine from rabbit platelets was first described by Barbaro and Zvaitler in I966. A soluble mediator between rabbit leukocytes and platelets was also detected by Siraganian and Osier in 1971. This factor was isolated and characterized in 1971 by Benveniste et al. and named platelet activating factor i PAF). It was shown to be released from rabbit basophils through an antigen - IgE-dependent mechanism. The presence of PAF in human leukocytes' and its aggregation and releasing effects on human platelets were also demonstrated. Chemical analysis has shown that PAF is a glycerophospholipid with a choline polar head group. an ester-linked acyl chain at the second carbon and a nonester link at the first carbon.' The structure of the mediator was found to be 1-O-alky1-2-acetyl-sn-glyceryl-3-phosphoryl choline and it has been chemically synthesized.""' A variable portion exists in the alkyl group attached to the first carbon which can have a variety of molecular sizes such as C and C (where Cu is more abundant). Recent work by Pinckard et al."" has shown that there are at least five variations of the alkyl group.PAF has been shown to have a broad range of biological effects. Release of PAF from alveolar macrophages may be important in asthma, allergy, and shock states. In a rabbit model of antigen IgE anaphylaxsis. PAF can induce all of the effects of antigen challenge and. therefore is presumed to be a key mediator in production of anaphylaxsis. In addition to aggregating and degranulating platelets it is a potent chemoattractant."" and causes contraction of guinea pig ileum contraction of lung tissue and enhanced capillary permeability PAF has important effects in the kidney and is also known as the renal hypotensive factor proposed by Blank et al. who found the structure of PAF independently of Benveniste et al.' In producing these responses. PAF acts by a receptor-like mechanism. In platelets. PAF selectively desensitizes itself but not thrombin or collagen. In smooth muscle tissues a similar phenomenon occurs with anaphylatoxin or other stimuli.In vivo. PAF probably acts in concert with other agents in producing its various biological effects. It causes platelets to release histamine serotonin and RCS (rabbit-contractile substance formed from prostaglandins PPG2, PGH2 and TXA2) which contracts rabbit aorta. PAF can cause cells to release SRS-A and leukotriene B."