BOTH MEMBRANE-BOUND AND SOLUBLE FORMS OF CD14 BIND TO GRAM-NEGATIVE BACTERIA

Tissue macrophages and their precursors - the blood monocytes - respon d rapidly to a bacterial infection with the release of inflammatory me diators. These mediators are involved in the recruitment of phagocytic cells, principally neutrophils, from the blood to the site of infecti on. To initiate this process macrophages and monocytes must be able to detect the presence of bacteria in a reliable, but nevertheless nonsp ecific, fashion. It is thought that this is achieved by means of recep tors on the cell surface which recognize structures common to many dif ferent bacteria. One candidate for such a ''pattern recognition elemen t'' is the cell surface glycoprotein CD14. CD14 has been shown to bind components of the Gram-positive cell wall and it also binds soluble l ipopolysaccharide released from Gram-negative bacteria. In both cases the interaction with CD14 leads to an activation of the cell. Here we show that human peripheral blood monocytes can, in addition, bind inta ct Gram-negative bacteria in the presence of serum and that this proce ss involves CD14. When CD14 expression is induced on the myelomonocyti c cell Line U937 by treatment with vitamin D3 the cells concomittently acquire the capacity to bind bacteria. Furthermore, a non-monocytic c ell line which does not bind bacteria acquires the capacity to do so w hen transfected with either the human or mouse CD14 gene. This binding can be inhibited by blocking the CD14 receptor with anti-CD14 antibod y or by blocking the ligand on the bacteria with soluble CD14. Finally we demonstrate binding of sCD14 to Escherichia coli. We conclude that in the presence of serum both membrane-bound and soluble forms of CD1 4 can bind to Gram-negative bacteria. This suggests that CD14 may play a role in the detection and elimination of intact bacteria in vivo.