Priming of human neutrophils by mycobacterial lipoarabinomannans: role of granule mobilisation

Lipoarabinomannans (LAMs) from mycobacteria were investigated concerning th eir effect on human neutrophils. Two types of LAM, the mannose-capped ManLA M from the virulent Mycobacterium tuberculosis H37Rv and the mannose-lackin g AraLAM from a rapidly growing mycobacterial strain were used. Neither Ara LAM nor ManLAM induced any significant direct activation of the NADPH-oxida se. Both LAMs, however, primed the neutrophils so that subsequent stimulati on with the peptide chemoattractants fMet-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-V al-DMet (WKYMVm) and the mammalian lactose-binding lectin galectin-3 result ed in a markedly enhanced oxidative response. The LAM-induced priming was a ccompanied by an increased exposure of complement receptors 1 and 3 as well as the formyl peptide receptor on the neutrophil surface, suggesting that the enhanced oxidative response could be due to upregulation of receptors o n the cell surface as a result of granule mobilisation. Since LAM-primed ne utrophils released 65% of the cell content of gelatinase but showed no incr eased release of vitamin B-12-binding protein, mobilisation of the gelatina se granules rather than the specific granules is concluded to be responsibl e for the priming effects. This is in agreement with the subcellular locali sation of receptors for fMLF, WKYMVm, as well as galectin-3, which are stor ed in the secretory vesicles and gelatinase granules. The priming effect ap peared very similar to that of Escherichia coli lipopolysaccharide, and sin ce no differences in activity could be detected between AraLAM and ManLAM, we hypothesize that the lipid anchor of the LAM is responsible for the prim ing effects. (C) 2001 Editions scientifiques et medicales Elsevier SAS.