COMPARISON OF THE REVERSED PASSIVE ARTHUS AND LOCAL SHWARTZMAN REACTIONS OF RABBIT SKIN - EFFECTS OF THE LONG-ACTING PAF ANTAGONIST UM-74,505

1 By using the selective, potent and long acting platelet-activating f actor (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 in flammatory responses induced by intradermally (i.d.) injected lipopoly saccharide (LPS), PAF, bradykinin and zymosan-activated plasma. 2 Neut rophil aggregation was assessed photometrically. Haemorrhage, oedema f ormation, platelet deposition and neutrophil accumulation were quantif ied in rabbit skill by measuring the accumulation of i.v. injected Cr- 51-labelled red blood cells (RBC), I-125-labelled human serum albumin, In-111-labelled platelets and In-111-labelled neutrophils respectivel y. 3 UK-74,505 inhibited in vitro neutrophil aggregation induced by PA F but not by leukotriene B-4. When injected i.v. into rabbits UK-74.50 5 suppressed oedema formation in response to i.d. PAF for up to 4 h bu t had no effect on oedema induced by bradykinin or zymosan-activated p lasma. 4 Oedema formation, but not neutrophil accumulation, produced d uring the RPA reaction was significantly inhibited by i.v. UK-74,505. The PAF antagonist also suppressed In-111-platelet but not In-111-neut rophil accumulation in response to i.d. LPS. UK-74.505 did not affect haemorrhage or oedema formation produced during the LPS-mediated LSR. 5 The results demonstrate that PAF is an important mediator of oedema formation, but not neutrophil accumulation. in the immune-complex medi ated RPA reaction in rabbit skin. PAF also appears to be required for platelet, but not neutrophil, accumulation in response to locally inje cted LPS. Our studies do not suggest a role for PAF in the LPS-mediate d LSR.