Serum amyloid P-component in murine tuberculosis: induction kinetics and intramacrophage Mycobacterium tuberculosis growth inhibition in vitro.
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.
Singh
Prati Pal
PP
National Institute of Pharmaceutical Education and Research, Phase-X, SAS Nagar-160 062, India. drppsingh2002@yahoo.com
Kaur
Sukhraj
S
D000818:Animals; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D006801:Humans; D016676:Macrophages, Alveolar / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development* / Q000472:pathogenicity*; D009569:Nitric Oxide / Q000096:biosynthesis; D000683:Serum Amyloid P-Component / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000382:microbiology; D015854:Up-Regulation
D000683:Serum Amyloid P-Component; D009569:Nitric Oxide