Influence of acyl and plasmalogenic analogs of platelet activating factor on chemotaxis of human leukocytes in vitro and their inflammatory and antiinflammatory activity in vivo.
The effects of platelet activating factor (PAF) and its cell analogs 1-O-alk-1;-enyl-2-acetyl-sn-glycero-3-phosphocholine (1-alkenyl-PAF) and 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-PAF) on chemotaxis of human leukocytes in vitro and their inflammatory and antiinflammatory activities in vivo were studied. Both analogs stimulated chemotaxis of human leukocytes in agarose gel. PAF and 1-alkenyl-PAF induced rat paw edema in the range of doses 0.1-10 and 10-100 micro g per paw, respectively. Paw edema induced by 1-acyl-PAF (10-100 micro g per paw) was more pronounced than that induced by PAF or 1-alkenyl-PAF. The latter also exhibited significant antiinflammatory effect by inhibiting PAF- or carrageenan-induced rat paw edema, and this effect exceeded that of dexamethasone. In these models of inflammation 1-acyl-PAF did not exhibit any antiinflammatory activity. The data suggest that PAF is not the only cell phospholipid mediating inflammation--its cell analogs, 1-acyl-PAF and 1-alkenyl-PAF, may also be involved into the inflammatory response. Possible interrelationships between cellular synthesis of 1-acyl-PAF, its formation in oxidized LDL, biological effects of lysolecithin, and penetration of LDL into the arterial wall are discussed.