The cholesterol content of the plasma membrane as a regulator of CD14 dependent signal transduction

Lipopolysaccharide (LPS) is known to bind to several surface molecules on various cells. The best characterized LPS-binding protein is CD14, strongly expressed in the majority of monocytes. Since CD14 is a glycosylphosphatidyl-inositol (GPI)-anchor protein without a cytoplasmic tail, it has been suggested that additional signalling receptors co-associate with CD14 in order to initiate signal transduction cascades. Here we show that after ligand binding in human blood monocytes, the b2-integrin CD11b/CD18 forms clusters with CD14, after ligand binding. Thus, in response to LPS stimulation a receptor complex is formed in the plane of the plasma membrane which may be of central importance for cellular responses to LPS. We also show that another physiologically relevant ligand of CD14, ceramide, which is structurally similar to LPS, induces a complex of CD14 and CD11b/CD18 after binding to CD14.