Induction of a macrophage migration enhancement factor after desensitization of tuberculin-positive rabbits with purified protein derivative

Abstract

The production of a macrophage migration enhancement factor (MEF) has been achieved as a consequence of administering a desensitizing dose of purified protein derivative (PPD) to Mycobacterium bovis BCGsensitized rabbits. The migration-enhancing effect was first demonstrated when alveolar macrophages (AM) harvested from desensitized rabbits exhibited marked migration stimulation; whereas maximum migration enhancement was observed 8 days after the administration of PPD, migration enhancement of the AM from these rabbits persisted for up to 12 days. Sera from BCG-sensitized, PPD-desensitized animals exhibited a peak of MEF activity 4 days after desensitization. Maximal MEF activity was demonstrated in culture supernatants of nonadherent spleen cells harvested 8 days after the intravenous desensitizing dose of PPD was given. Control spleen cell culture supernatants did not produce detectable MEF. The route of desensitization with PPD was critical. When PPD was administrated intratracheally, MEF activity was not induced. The intravenous administration of BCG after PPD desensitization reversed migration enhancement to strong migration inhibition. Ammonium sulfate fractionation indicated that two fractions contained MEF activity. MEF activity was retained by dialysis membranes with a 15,000-molecular-weight cutoff but passed through dialysis membranes with a 25,000-molecular-weight cutoff. The mixture of migration inhibition factor with MEFcontaining supernatants resulted in the mutual cancellation of both activities. These observations suggest that MEF may be a modulator of macrophage effector responses mediated by migration inhibition factor.