ABSTRACT

Carole Delmas, Anne Venisse, Alain Vercellone, Martine Gilleron, Renaud Albigot, Therese Brando, Michel Riviere, and Germain Puzo

National Center fo r Scientific Research, Toulouse, France

I. INTRODUCTION

Lipoarabinomannans (LAM) are ubiquitous components of the mycobacte­ rial cell walls [1]. According to their structures, LAM are classified in two types, namely, AraLAM and ManLAM. AraLAM were first isolated from an unidentified fast growing mycobacterial species [2], whereas ManLAM were found in slow growing strains such as Mycobacterium tuberculosis, Erdman strain [3,4], and in the Mycobacterium bovis BCG (Bacille Calmette-Guerin) [5,6] vaccine. The structural models of AraLAM and Man­ LAM reveal that they are composed of two homopolysaccharides, namely, the D-mannan and the D-arabinan (Fig. 1). The mannan is a linear oligo­ saccharide composed by 6-O-linked o:-D-Man/?s (mannopyranose) with side chains containing one single unit of a-D-Man/? attached at the position C2. At its reducing end, this mannan core is glycosylated by the phosphatidyl myo-Ins (inositol) anchor. Three major structural motifs composed the D-arabinan: (1) a linear oligosaccharide of 5-O-linked a-D-Ara/(arabinofuranose), (2) side chains attached via the C3, and finally, (3) terminal disaccharidic unit of /3-D-Ara/-(l -► 5)-a-D-Ara/ -► . The major struc­ tural difference between AraLAM and ManLAM is the presence of small mannooligosaccharide units capping the arabinan side chains of the Man­ LAM (Fig. 1). More recently, though, it was established that AraLAM from an unidentified fast growing mycobacterial species [2,7] and from Mycobacterium smegmatis (unpublished results) contain phosphoinositide caps. The AraLAM and ManLAM present a large spectrum of immunologi­ cal activities. Some of these activities are specific. For example, ManLAM bind murine and human macrophages via the mannose receptor [8,9] and activate human lymphocyte Ta/3 CD4 “ CD8 “ [10], whereas AraLAM stim­ ulate the precoce genes of the macrophage activation [11,12] as well as the

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Figure 1 Structural model of ManLAM and AraLAM.