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*
Department of Cell Biology and Immunology, Vrije Universiteit, Amsterdam, The Netherlands;
Sir William Dunn School of Pathology, Oxford, United Kingdom; and
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
The scavenger receptors expressed by macrophages are thought to
play an important role in the immune response against bacteria by
mediating binding and phagocytosis. A novel member of the class A
scavenger receptor family, macrophage receptor with collagenous
structure (MARCO), has recently been identified. In this study we have
generated a panel of mAbs with specificities for different domains of
this receptor. Two of those reacting with the C-terminal cysteine-rich
domain block ligand binding of MARCO. The in vivo expression of this
murine receptor is normally restricted to distinct populations of
macrophages in the spleen and lymph nodes. During bacillus
Calmette-Guérin (BCG) infection, during bacterial sepsis, or
after the injection of purified LPS, however, the expression of MARCO
is rapidly induced on macrophages in other tissues, including Kupffer
cells in the liver. Using the mouse macrophage cell line J774.2, it was
shown that LPS stimulation up-regulates surface expression of MARCO in
a dose- and time-dependent fashion. The proinflammatory cytokines IL-1,
IL-6, TNF-
, and IFN-
had little or no effect. Using inhibitory
mAbs, the relevance of MARCO for the clearance of circulating bacteria
in vivo was determined. Although the overall elimination of live
Escherichia coli and Staphylococcus
aureus from the blood did not appear to be affected by
treatment with these Abs, the capturing of heat-killed bacteria by
macrophages in the marginal zone areas of the spleen was clearly
inhibited. This study suggests a role for MARCO in the host
antibacterial defense.
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