Acute-phase reactants during murine tuberculosis: unknown dimensions and new frontiers.
METHODS
Serum amyloid P-component (SAP) plays important roles in host defense during various infectious diseases; however, nothing is known in tuberculosis (TB).


OBJECTIVE
To study the SAP response of Mycobacterium tuberculosis H37Rv- and H37Ra-infected mice, and to determine the effect(s) of purified mouse SAP both on their intra-alveolar macrophage (AM) uptake and intra-AM growth in vitro.


METHODS
The SAP levels of mice intratracheally infected with M. tuberculosis H37Rv and H37Ra were determined by ELISA. Mycobacterial AM uptake and intra-AM growth in vitro were determined using fluorescence microscopy and plating, respectively.


RESULTS
M. tuberculosis H37Rv-infected mice showed significantly (p < 0.05) increased SAP levels (352.8+/-36.1 microg/ml) with compared mice infected with M. tuberculosis H37Ra (170+/-18.5 microg/ml). During the acute phase of both these infections, enhanced SAP levels correlated with the lung mycobacterial load. In vitro, purified mouse SAP (1-80 microg/ml) inhibited the AM uptake of both the mycobacteria in a concentration-dependent manners to a similar extent; 20 microg/ml SAP appeared optimal. Mycobacterial uptake inhibition was divalent cation- and pH-dependent, and was unaffected both by heat-inactivated and deglycosylated SAP, separately. Curiously, purified mouse SAP (1-80 microg/ml), in a concentration-dependent manner, inhibited the intra-AM growth of both M. tuberculosis H37Rv and H37Ra in vitro; the effect was 0.8 log10 CFUs greater on the latter. Both the mannose-based simple sugars and rabbit anti-mouse SAP polyclonal antibody, separately, annulled the inhibition of mycobacterial growth in vitro.


CONCLUSIONS
This initial study demonstrates that both the SAP response of M. tuberculosis-infected mice, and the SAP-induced intra-AM mycobacterial growth inhibition in vitro were apparently dependent on mycobacterial virulence.
Singh
Prati Pal
PP
National Institute of Pharmaceutical Education and Research, Phase-X, S.A.S Nagar-160 062, India. drppsingh2002@yahoo.com
Kaur
Sukhraj
S
D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003114:Colony-Forming Units Assay; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis; D009569:Nitric Oxide / Q000097:blood; D000683:Serum Amyloid P-Component / Q000032:analysis*; D014376:Tuberculosis / Q000276:immunology*
D015415:Biomarkers; D000683:Serum Amyloid P-Component; D009569:Nitric Oxide