On the biological role of lipid chemotactic factors.

Abstract

Our experimental data of the past seven years cover the generation of a non-preformed lipid-mediator which primarily assayed with guinea pig eosinophils proved to be eosinophil chemotactic. The analysis of the various stimuli led in 1978 to the concept of the phospholipase-arachidonic sequence as a common link for membrane activation. Immunopharmacological studies using either arachidonic acid as stimulus or arachidonic acid analogues provided an early evidence that the lipid chemotactic factor was a lipoxygenase product. These results were supported by analytical studies using thin layer chromatography, reversed phase HPLC, mass spectrometry, the comparison of the lipid chemotactic factor with endogeneous HETEs and by the synthesis of mono- and di-HETEs. It became also evident that mono- and di-HETE are not only mediators but also modulators of inflammatory reactions as was demonstrated for the C5a induced eosinophil chemotactic response. A less pronounced effect on the C5a induced eosinophil and neutrophil chemotactic response was exerted by PAF and its structural analogues. It is also demonstrated that isolated bacterial exotoxins trigger the cells via the phospholipase-arachidonic acid sequence thus generating mono- and di-HETEs leading to the amplification of an inflammatory response.