CD14 explained

CD14 (cluster of differentiation 14) is a human protein made mostly by macrophages as part of the innate immune system.[1] [2] It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP).

CD14 exists in two forms, one anchored to the membrane by a glycosylphosphatidylinositol (GPI) tail (mCD14), the other a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 kDa) or is directly secreted from intracellular vesicles (56 kDa).[3]

The x-ray crystal structure of human CD14 reveals a monomeric, bent solenoid structure containing a hydrophobic amino-terminal pocket.[4]

CD14 was the first described pattern recognition receptor.

Function

CD14 acts as a co-receptor (along with the Toll-like receptor TLR 4 and MD-2) for the detection of bacterial lipopolysaccharide (LPS).[5] [6] CD14 can bind LPS only in the presence of lipopolysaccharide-binding protein (LBP).Although LPS is considered its main ligand, CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid.[7] Cluster of differentiation CD14 is areceptor for a very wide range of microbial products including lipopolysaccharide (released from Gram-negative bacteria), peptidoglycans, and lipoteichoic acid (constituents of Gram-positive bacteria).[8]

Tissue distribution

CD14 is expressed mainly by macrophages and (at 10-times lesser extent) by neutrophils. It is also expressed by dendritic cells. The soluble form of the receptor (sCD14) is secreted by the liver and monocytes and is sufficient in low concentrations to confer LPS-responsiveness to cells not expressing CD14. mCD14 and sCD14 are also present on enterocytes.[9] sCD14 is also present in human milk, where it is believed to regulate microbial growth in the infant gut.

Differentiation

CD14+ monocytes can differentiate into a host of different cells, including dendritic cells, a differentiation pathway encouraged by cytokines, including GM-CSF and IL-4.

Interactions

CD14 has been shown to interact with lipopolysaccharide-binding protein.[10] [11]

Notes and References

  1. Setoguchi M, Nasu N, Yoshida S, Higuchi Y, Akizuki S, Yamamoto S . Mouse and human CD14 (myeloid cell-specific leucine-rich glycoprotein) primary structure deduced from cDNA clones . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1008 . 2 . 213–222 . July 1989 . 2472171 . 10.1016/0167-4781(80)90012-3 .
  2. Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B . Monocyte antigen CD14 is a phospholipid anchored membrane protein . Blood . 73 . 1 . 284–289 . January 1989 . 2462937 . 10.1182/blood.V73.1.284.284 . free .
  3. Kirkland TN, Viriyakosol S . Structure-function analysis of soluble and membrane-bound CD14 . Progress in Clinical and Biological Research . 397 . 79–87 . 1998 . 9575549 .
  4. Kelley SL, Lukk T, Nair SK, Tapping RI . The crystal structure of human soluble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket . Journal of Immunology . 190 . 3 . 1304–1311 . February 2013 . 23264655 . 3552104 . 10.4049/jimmunol.1202446 .
  5. Kitchens RL . Role of CD14 in cellular recognition of bacterial lipopolysaccharides . Chemical Immunology . 74 . 61–82 . 2000 . 10608082 . 10.1159/000058750 . 3-8055-6917-3 . Chemical Immunology and Allergy .
  6. Tapping RI, Tobias PS . Soluble CD14-mediated cellular responses to lipopolysaccharide . Chemical Immunology . 74 . 108–121 . 2000 . 10608084 . 10.1159/000058751 . 3-8055-6917-3 . Chemical Immunology and Allergy .
  7. Ranoa DR, Kelley SL, Tapping RI . Human lipopolysaccharide-binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to Toll-like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex . The Journal of Biological Chemistry . 288 . 14 . 9729–9741 . April 2013 . 23430250 . 3617275 . 10.1074/jbc.M113.453266 . free .
  8. De Maio A, Torres MB, Reeves RH . Genetic determinants influencing the response to injury, inflammation, and sepsis . Shock . 23 . 1 . 11–17 . January 2005 . 15614125 . 10.1097/01.shk.0000144134.03598.c5 . 35306289 . free .
  9. Funda DP, Tucková L, Farré MA, Iwase T, Moro I, Tlaskalová-Hogenová H . CD14 is expressed and released as soluble CD14 by human intestinal epithelial cells in vitro: lipopolysaccharide activation of epithelial cells revisited . Infection and Immunity . 69 . 6 . 3772–3781 . June 2001 . 11349042 . 98389 . 10.1128/IAI.69.6.3772-3781.2001 .
  10. Thomas CJ, Kapoor M, Sharma S, Bausinger H, Zyilan U, Lipsker D, Hanau D, Surolia A . 6 . Evidence of a trimolecular complex involving LPS, LPS binding protein and soluble CD14 as an effector of LPS response . FEBS Letters . 531 . 2 . 184–188 . November 2002 . 12417309 . 10.1016/S0014-5793(02)03499-3 . 25135963 .
  11. Yu B, Wright SD . LPS-dependent interaction of Mac-2-binding protein with immobilized CD14 . Journal of Inflammation . 45 . 2 . 115–125 . 1995 . 7583357 .

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