DIFFERENTIAL RESPONSES OF HUMAN MONONUCLEAR PHAGOCYTES TO MYCOBACTERIAL LIPOARABINOMANNANS - ROLE OF CD14 AND THE MANNOSE RECEPTOR

CD14 is a signaling receptor for both gram-negative bacterial lipopoly saccharide (LPS) and mycobacterial lipoarabinomannan (LAM) that lacks terminal mannosyl units (AraLAM). In contrast, terminally mannosylated LAM (ManLAM) binds the macrophage mannose receptor (MMRc), although t he ability of the MMRc to serve as a signaling receptor has not been p reviously reported. We compared the abilities of AraLAM and ManLAM to induce distinct responses in two monocytic cell populations, freshly i solated human peripheral blood monocytes (PBM) and monocyte-derived ma crophages (MDM). The responses examined were chemotaxis and transient changes in free cytosolic calcium ([Ca2+](in)). We found that AraLAM b ut not ManLAM was chemotactic for both PBM and MDM, Migration of these cells in vitro to AraLAM mas specifically blocked by an anti-CD14 mon oclonal antibody, suggesting that CD14 mediates the chemotactic respon se to AraLAM. Subsequently, we found that AraLAM induced a transient r ise in [Ca2+](in) levels within a subpopulation of PBM but not MDM. Th is response was blocked by anti-CD14 antibodies, In contrast, ManLAM i nduced a transient rise in [Ca2+](in) levels within a subpopulation of MDM but not PBM. This response was blocked by either anti-CD14 or ant i-MMRc antibodies. These data suggest that the MMRc can serve as a sig naling receptor and that coligation of both CD14 and the MMRc is requi red to elicit a specific response, Thus, one response to LAM (chemotax is) can be elicited solely by engaging CD14, whereas a different respo nse (changes in [Ca2+](in) levels) depends on both the differentiation state of the cells and concomitant engagement of CD14 and the MMRc.