Surface Properties of Activated Macrophages: Sensitized Lymphocytes, Specific Antigen and Lymphokines Reduce Expression of Antigen F4/80 and FC and Mannose/Fucosyl Receptors, but Induce Ia

Abstract

The term macrophage activation was introduced by Mackaness in the 1960’s to describe the enhanced microbicidal activity of macrophages from animals with acquired immunity to infection with facultative intracellular pathogens (1). Attempts have been made since that time to define the properties of macrophage activation in terms of morphological changes, biochemical or membrane events and correlate these with microbicidal and tumoricidal activity (2,3,4). After infection with bacillus Calmette-Guérin (BCG), the host may acquire immunity to specific secondary challenge, protection against unrelated virulent organisms such as Listeria monocytogenes and increased resistance to transplantable tumors (5–7). Macrophages from such animals spread rapidly in cultures, secrete high levels of hydrogen peroxide (8) and plasminogen activator (9) and display enhanced tumoricidal activity (10). We have shown that infection of the mouse peritoneal cavity by BCG markedly alters the surface properties of the macrophages induced, compared with uninfected controls, or after injection of thioglycollate broth (11). Quantitative binding assays with radio-labeled ligands or monoclonal antibodies showed that BCG-activated peritoneal macrophages (BCG-PM) express reduced antigen F4/80, (a macrophage specific antigen of MW 160,000), Fc receptors and mannose specific receptor activity, but have enhanced Ia antigen and increased secretion of hydrogen peroxide and plasminogen activator. We have also shown that (a) these alterations in the plasma membrane make it possible to distinguish between activated and non-activated macrophages, and (b) all changes of macrophage activation by BCG are dependent upon ‘T’ lymphocytes and specific antigen. However, studies with nude mice indicate that the activation phenotype may also arise by an independent pathway. The altered surface properties are stable, occur in a co-ordinate manner, independent of a particular agent and can be induced in vivo and in vitro.