Serum amyloid P-component (SAP), a pentraxin, is known to play an important role in innate immunity to microbial
infections; however, nothing is known about it during
tuberculosis (TB). Mice intratracheally infected with Mycobacterium tuberculosis Erdman, showed peak SAP levels (442+/-58.2 microg/ml) on day 21, which declined to background levels by day 60. Their serum
interleukin-6 levels paralleled SAP levels, whereas, their serum
transforming growth factor-beta levels were paradoxical. During the acute phase of
infection, the SAP levels positively correlated with the lung mycobacterial load. Purified mouse SAP (1-50 microg/ml) treatment of M.
tuberculosis-infected alveolar macrophages (AMs), in vitro, inhibited their intracellular mycobacterial growth; maximum inhibition (1.1 log10 CFU reduction) occurred
at 10 microg/ml, and a 4-day treatment appeared optimal. Treatment of AMs with both rabbit anti-mouse SAP polyclonal antibody and
mannose-derived
simple sugars, separately, blocked the SAP-induced inhibition of mycobacterial growth. The mycobacterial growth inhibition appeared to be
nitric oxide (NO)-dependent as
NO synthase inhibitors, both
aminoguanidine and N(G)-monomethyl-
L-arginine, annulled it. Further, SAP treatment of infected AMs induced significant (P<0.05) elaboration of
nitrite (72.1+/-8.3 nM/ml), compared to the controls, and these AMs showed augmented expression of inducible
NO synthase. This first study demonstrates that during murine TB the SAP levels were increased, and purified mouse SAP inhibited the intra-AM M.
tuberculosis growth, in vitro, apparently via NO-dependent mechanism(s). SAP may thus contribute both to the pathogenesis and pulmonary innate immunity in TB.