Self-enhancement of phagocytosis by murine resident peritoneal macrophages and its relationship to morphine effects on the process.

Abstract

Macrophages are an important component of the immune system since they are part of both innate and cellular immune responses (Rooijen and Sanders, 1997). It is well documented that macrophage activation results in enhancement of antimicrobial and antitumoral activities in these cells. For example, upon activation, macrophages can become engaged in the clearance of microorganisms or altered self-material by enhanced oxidative burst, chemotaxis, phagocytosis, intracellular killing and cytokine secretion (Peterson et al, 1998; Dearman et al, 1996, Tachibana et al., 1992, Langermans et al, 1990). One important factor that can also modulate immune cell functions is exposure to opioids. Enkephalins, endorphins and morphine-like opioids are capable of influencing the immune system through its binding to opioid receptors (Eisenstein et al., 1998). In our laboratory we have shown that in vitro morphine can inhibit Fc-mediated phagocytosis by thioglycolate-elicited murine peritoneal macrophages (Casellas et al., 1991; Tomei and Renaud, 1997). In these cells the response to acute exposure to morphine is biphasic, since inhibition is not observed at low or high doses. We have also shown that upon chronic exposure to morphine macrophage phagocytosis becomes insensitive to the drug, suggesting that a state akin to tolerance is developed in these cells. Furthermore, morphine withdrawal from putatively tolerant cells results in inhibition of phagocytosis (Tomei and Renaud, 1997; Lazaro et al., 1999). This latter observation suggests that chronically exposed macrophages may be in a dependent state, since they seem to need morphine to phagocytize at a control level. The tolerant state can be prevented if the cells are simultaneously incubated with both morphine and naloxone, which suggests that development of the tolerant/dependent state is mediated through classic opioid receptors (Lazaro et al., 1999). Other investigators have demonstrated that thioglycolate-elicited cells show an altered response to other stimuli, when compared to resident macrophages. For example, thioglycollate treatment can increase the production of cytokines, such as (Tachibana et al., 1992). However, no thorough studies have been performed to determine