Comparison of the reversed passive Arthus and local Shwartzman reactions of rabbit skin: effects of the long-acting PAF antagonist UK-74,505.
1. 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. 2. 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 51Cr-labelled red blood cells (RBC), 125I-labelled human serum albumin, 111In-labelled platelets and 111In-labelled neutrophils respectively. 3. UK-74,505 inhibited in vitro neutrophil aggregation induced by PAF but not by leukotriene B4. 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. 4. 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 111In-platelet but not 111In-neutrophil 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 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.
Norman
K E
KE
Department of Applied Pharmacology, Imperial College of Medicine, National Heart & Lung Institute, London.
Williams
T J
TJ
Rossi
A G
AG
D000818:Animals; D001183:Arthus Reaction; D002449:Cell Aggregation / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011817:Rabbits; D012790:Shwartzman Phenomenon
D004095:Dihydropyridines; D007093:Imidazoles; D010972:Platelet Activating Factor; C073027:modipafant