Mononuclear phagocytes increasingly appear to have a central regulatory role in governing in~lammatory and immune responses. The concept of macrophage activation dates from Metchnikoff who noted that mononuclear phagocytes from animals resistant to bacterial challenge had perfected their powers of phagocytosis and microbicidal destruction. This classical view places the macrophage in the efferent part of the immune system. More recently it has been shovn that macrophagcs are cruciallY involved in the regulation of lymphocyte f~~ction, thus playing a~ important role in the afferent part of the imm~~e system. Chapter 1 briefly summarizes the role of macrophages in immunity, the mechanisms leading to macrophage activation and alterations in macrophage metabolism and chemistry that accompany these cha~ges. Multiple signals from the extracellular milieu act on macrophages to regulate activation. In turn, the numerous secretory products of macrophages act on the environment. Among these products are arachidonic acid derived metabolites (chapter 2) which play a profound role in dictating the progression of immune events. For example, various hydroxyeicosatetraenoic acids and leukotriene B4 are extremely potent in regulating the functions of neutrophile, the hallmark of acute inflammatory mechanisms. In addition, specific prostaglandins have been shown to modulate the function of macrophages and suppress a variety of inflammatory or immune related processes. For example. earlier observations in our laboratory showed that prostaglandins of the E-series inhibited the development of the macrophage mediated proliferative component of an inflammatory reaction. They further indicated that this inhibition was realized via stimulation of macrophage cyclic AMP synthesis. In chapter 3 the mechanisms, by which alterations in cyclic AMP content a~fect macrophage activity are briefly summarized. The findings described in the previous paragraph led to the experiments described 1n this thesis. which are aimed at unravelling the interaction of various arachidonic acid oxygenation products with regard to the regulation of macrophage activity.

The experiments described in this thesis would not have been possible without the generous gifts of leukotriene C 4 from Dr. J. Rokach, Merck Frosst laboratories, canada Financial support by the Netherlands Astma Foundation for the publication of this thesis is greatfully acknowledged.
I.L. Bonta
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Schenkelaars, E. J. (1985, November 27). Regulation of macrophage activity by eicosanoids . Retrieved from