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

• Published in: Biochemistry (Moscow) 2002-11, Vol.67 (11), p.1248-1252
• Main Authors: Kulikov, V I, Muzya, G I
• Format: Article
• Language: English
• Subjects: Acylation; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological effects; Carrageenan - antagonists & inhibitors; Carrageenan - toxicity; Cattle; Chemotaxis, Leukocyte - drug effects; Disease Models, Animal; Edema; Edema - immunology; Edema - metabolism; Edema - pathology; Hindlimb - pathology; Humans; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Leukocytes - cytology; Leukocytes - immunology; Leukocytes - metabolism; Plasmalogens - chemistry; Plasmalogens - metabolism; Platelet Activating Factor - analogs & derivatives; Platelet Activating Factor - antagonists & inhibitors; Platelet Activating Factor - metabolism; Platelet Activating Factor - pharmacology; Rats; Rats, Wistar; Rodents; Time Factors
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1023/A:1021349304885

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.