Serum amyloid P-component-mediated inhibition of the uptake of Mycobacterium tuberculosis by macrophages, in vitro

Abstract

The effect of purified mouse serum amyloid P-component (SAP) treatment of mouse alveolar macrophages (AMs) on their uptake of Mycobacterium tuberculosis Erdman was investigated, in vitro. SAP (0.5-50.0 μg/ml), in a concentration-dependent manner, inhibited the M. tuberculosis uptake by the AMs; maximum inhibition (33.43%) occurred at 10.0 μg/ml. The inhibition of uptake could be observed as early as 30 min after the incubation of AMs with 10.0 μg/ml SAP; however, an incubation of 60 min induced maximum inhibition beyond which the response became static. The SAP-mediated decreased uptake of M. tuberculosis also resulted in their reduced intramacrophage growth as determined by colony-forming unit counts. SAP inhibited the uptake of mycobacteria in the presence of Ca2+, and at pH = 5.6, the inhibition was abrogated. Deglycosylation of purified SAP with N-glycanase, and not with O-glycanase, blocked the SAP-mediated inhibition of the uptake. Heat-inactiva ted (80°C; 1 h; pH 7.0) SAP did not inhibit the uptake of M. tuberculosis by AMs. These data, apparently for the first time, indicate that purified mouse SAP, in a divalent cation- and N-linked oligosaccharide glycosyladon-dependent manner, inhibited the in vitro uptake of M. tuberculosis Erdman by mouse AMs, which was also associated with their reduced intracellular growth.