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Comparison of the reversed passive Arthus and local Shwartzman reactions of rabbit skin: effects of the long‐acting PAF antagonist UK‐74,505
Author(s) -
Norman Keith E.,
Williams Timothy J.,
Rossi Adriano G.
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701057
Subject(s) - platelet activating factor , chemistry , arthus reaction , zymosan , antagonist , lipopolysaccharide , platelet , bradykinin , in vitro , pharmacology , leukotriene b4 , immunology , medicine , inflammation , biochemistry , receptor
By using the selective, potent and long acting platelet‐activating factor (PAF) antagonist, UK‐74,505, we investigated the role of PAF in a local Shwartzman reaction (LSR) and a reversed passive Arthus (RPA) reaction in rabbit skin. For comparison, we also studied the effect of the PAF antagonist on neutrophil aggregation in vitro and on acute inflammatory responses induced by intradermally (i.d.) injected lipopolysaccharide (LPS), PAF, bradykinin and zymosan‐activated plasma. Neutrophil aggregation was assessed photometrically. Haemorrhage, oedema formation, platelet deposition and neutrophil accumulation were quantified in rabbit skin by measuring the accumulation of i.v. injected 51 Cr‐labelled red blood cells (RBC), 125 I‐labelled human serum albumin, 111 In‐labelled platelets and 111 In‐labelled neutrophils respectively. UK‐74,505 inhibited in vitro neutrophil aggregation induced by PAF but not by leukotriene B 4 . When injected i.v. into rabbits UK‐74,505 suppressed oedema formation in response to i.d. PAF for up to 4 h but had no effect on oedema induced by bradykinin or zymosan‐activated plasma. Oedema formation, but not neutrophil accumulation, produced during the RPA reaction was significantly inhibited by i.v. UK‐74,505. The PAF antagonist also suppressed 111 In‐platelet but not 111 In‐neutrophil accumulation in response to i.d. LPS. UK‐74,505 did not affect haemorrhage or oedema formation produced during the LPS‐mediated LSR. The results demonstrate that PAF is an important mediator of oedema formation, but not neutrophil accumulation, in the immune‐complex mediated RPA reaction in rabbit skin. PAF also appears to be required for platelet, but not neutrophil, accumulation in response to locally injected LPS. Our studies do not suggest a role for PAF in the LPS‐mediated LSR.British Journal of Pharmacology (1997) 120 , 1286–1293; doi: 10.1038/sj.bjp.0701057