Clearance and organ distribution of Mycobacterium tuberculosis lipoarabinomannan (LAM) in the presence and absence of LAM-binding immunoglobulin M

Lipoarabinomannan (LAM) is a component of the mycobacterial surface which h as been associated with a variety of deleterious effects on immune system f unction. Despite the importance of LAM to the pathogenesis of mycobacterial infection, there is no information available on its fate in vivo. In this study, we determined the pharmacokinetics and tissue distribution of exogen ously administered LAM in mice. For measurements of serum and tissue LAM co ncentrations, we developed an enzyme-linked immunosorbent assay which used monoclonal antibodies of different isotypes to capture and detect LAM at co ncentrations of greater than or equal to 0.4 mu g/ml. Intravenous administr ation of LAM to mice resulted in transient serum levels with organ depositi on in the spleen and in the liver, Immunohistochemical studies localized LA M to the spleen marginal zone macrophages and, to a lesser degree, to liver macrophages. When LAM was administered to mice previously given a LAM-bind ing immunoglobulin M (IgM), LAM was very rapidly cleared from circulation. In those mice, deposition of LAM in the spleen was significantly reduced wh ile LAM deposition in the liver increased, Administration of LAM-binding Ig M resulted in significant levels of IgM to LAM in bile consistent with an i ncreased hepatobiliary excretion of LAM in the presence of specific antibod y, Bile, liver extracts, and bile salts were found to rapidly inactivate th e immunoreactivity of LAM, The results indicate that serum clearance and or gan deposition of LAM in mice are affected by the presence of LAM-binding a ntibody and suggest a mechanism by which antibody could modify the course o f mycobacterial infection.