MACROPHAGE BEHAVIOR ASSOCIATED WITH ACUTE AND CHRONIC EXPOSURE TO HIVGP120, MORPHINE AND ANANDAMIDE - ENDOTHELIAL IMPLICATIONS

We demonstrate that immediate exposure to gp120 (5 min; 0.1 mu g/ml) r esults in a significant shift of the macrophage population to an amoeb oid and motile category (P<0.01; 91.7 +/- 5.5 vs. a control value of 4 2.4 +/- 4.2) and prior exposure with anti-gp120 antagonizes this shift . Acute exposure of the macrophages to morphine (10(-6) M) or anandami de (10(-6) M) resulted in the cells rounding up (shape factors of 0.84 and 0.87 respectively) and becoming non-motile. The action is blocked by prior treatment with the specific antagonists naloxone and SR 1417 16A. Chronic exposure (6 h) of the cells to all three agents resulted in a random migration pattern. Further, all agents blocked chemotaxis induced by DAMA and IL-1. Observation of the cells behavior during chr onic exposure revealed a sporadic activity pattern with gp120 whereas morphine and anandamide first induced a period of inactivity which is followed by a period of activity (chemokinesis). Recent work from our laboratory has demonstrated that both morphine and anandamide acutely stimulate constitutive macrophage nitric oxide (NO) release, which the n induces macrophagre rounding and inactivity. It was therefore of int erest to examine their behavior by exposing macrophages to the NO-dono r SNAP. In a concentration dependent manner SNAP exhibited the same be havioral actions as both substances of abuse. Given this, we next dete rmined if macrophages exposed to gp120 would release NO. We demonstrat ed that NO was released only when exposed to morphine and anandamide n ot gp120. Thus. the chemokinetic inducing activities of these agents m ay be the basis for excitotoxin liberation in neural tissues and/or a higher viral load in various organ systems since cellular adherence an d random migration are stimulated. (C) 1998 Elsevier Science Ireland L td.