THE 25-KDA SOLUBLE CD23 ACTIVATES TYPE-III CONSTITUTIVE NITRIC OXIDE-SYNTHASE ACTIVITY VIA CD11B AND CD11C EXPRESSED BY HUMAN MONOCYTES

CD23, a low-affinity receptor for IgE, was recently shown to bind to C D11b and CD11c molecules on human monocytes, The 25-kDa soluble fragme nt of CD23 (sCD23), was tested for its capacity to elicit various sign aling pathways in human monocytes, sCD23 was found to trigger an early increase in cGMP accumulation, through the generation of nitric oxide , This was a result of activating the L-arginine pathway, since the sC D23-mediated effect was inhibited in the presence of substituted nonme tabolizable L-arginine analogues, In addition, the increase in cGMP wa s suppressed by calcium chelators and inhibitors of the calcium/calmod ulin complex, suggesting the involvement of a constitutive, calcium-de pendent nitric oxide synthase (NOS), Indeed, the presence of an endoth elial constitutive type III NOS mRNA was detected in nonactivated huma n monocytes, and the corresponding protein has been detected by flow c ytometry, Moreover, sCD23 was shown to induce a calcium influx in mono cytes, in accordance with an activation of a constitutive NOS through a transient increase in [Ca2+](i). As expected, these events were mimi cked by mAbs against CD11b and CD11c, the macrophage receptors for CD2 3, In addition to these early events, sCD23 and the agonistic anti-CD1 1b and CD11c mAbs, which all trigger the release of proinflammatory me diators such as TNF-alpha, were shown to act through an NO-dependent p rocess.