CD14:LPS binds CR3

Stable Identifier
Homo sapiens
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Upon LPS stimulation, CD14, in addition to promote endotoxin transfer to TLR4, also triggers complement receptor 3 (CR3) activation [Troelstra A et al 1999; Kagan JC and Medzithov R 2007]. LPS-mediated CR3 upregulation results in induction of PIP5K-dependent de novo synthesis of PIP2 in the lipid rafts through the phosphorylation of PI(4)P. Mal(TIRAP) is then recruited at the site of the newly generated PIP2 where it binds TLR4 via the TIR domain. Finally, MyD88 is recruited to the activated TLR4-CD14 complex via the TIRAP molecule and initiates a signaling cascade leading to a first wave of NF-kB activation from the plasma membrane [Kagan JC and Medzithov R 2007].

CR3 (CD11b/CD18) is a member of CD18 receptor family of cell surface glycoproteins, which are expressed in human phagocytes. Each of the three receptors (CR3, lymphocyte function-associated antigen LFA-1, and p150-95) is a heterodimer composed of a beta-chain (CD18) that is identical in all three receptors and a noncovalently associated alpha chain (CD11) that is unique to each molecule [ . CR3 is known as a receptor for the surface-bound complement protein C3bi, but it has been also reported to recognize several other ligands, including bacterial patterns such as LPS and lipid A. Two distinct binding sites on CR3 have been described: 1) a protein-binding-site that binds C3bi, fibrinogen, and Leishmania glycoprotein 63, and 2) a lipid- binding-site involved in the binding of LPS, lipid A [Wright SD et al 1989; Van Strijp J.A.G et al 1993].

CR3, LFA-1 and p150-95 have been reported to mediate not only LPS interaction but also promote the binding of Escherichia coli to human macrophages [Wright SD and Jong MTC 1986].

Literature References
PubMed ID Title Journal Year
10201950 Lipopolysaccharide-coated erythrocytes activate human neutrophils via CD14 while subsequent binding is through CD11b/CD18

van Bommel, T, Troelstra, A, Van Strijp, JA, de Graaf-Miltenburg, LA, Van Kessel, KP, Verhoef, J

J. Immunol. 1999
3537192 Adhesion-promoting receptors on human macrophages recognize Escherichia coli by binding to lipopolysaccharide

Jong, MT, Wright, SD

J. Exp. Med. 1986
2462607 CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-Asp-containing peptides and a second site for bacterial lipopolysaccharide

Jong, MT, Chad, Z, Kabbash, LG, Wright, SD, Levin, SM

J. Exp. Med. 1989
16751103 Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling

Kagan, JC, Medzhitov, R

Cell 2006
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