Inhibition of Immune Complex-Induced Inflammation by A small Molecular Weight Selectin Antagonist.
The anti-inflammatory effect of a small molecular weight antagonist of P- and E-selectin-dependent cell adhesion was examined. The glycolipid sulphatide was shown to block the adherence of thrombin-activated rat platelets to HL-60 cells. This interaction is known to be dependent on P-selectin. The rat dermal reverse passive Arthus reaction was used to assess the effect of sulphatide on a neutrophil dependent inflammatory response. Sulphatide dosedependently blocked both the vascular permeability increase and cell infiltration after intraperitoneal administration. These results show that a small molecular weight compound which blocks P- and E-selectin dependent adhesion in vitro can effectively block the inflammation due to immune complex deposition. A compound with this type of profile may have therapeutic potential in the treatment of immune complex mediated diseases.
Nair
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Bristol-Myers Squibb Pharmaceutical Research Institute 100 Forest Avenue Buffalo NY 14213 USA.
Todderud
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Davern
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Lee
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D
Aruffo
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A
Tramposch
K M
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