Disease relevance of CD14

• Immune cells detect E. coli by Toll-like receptor 4 (TLR4) binding its pathogenic ligand, lipopolysaccharide (LPS), although signaling requires accessory molecules such as CD14 [1].
• CD14, the leukocyte co-receptor for lipopolysaccharide (LPS), is important in the response of bovine polymorphonuclear neutrophil leukocytes (PMN) to Gram-negative bacteria [2].
• Recombinant bovine soluble CD14 reduces severity of experimental Escherichia coli mastitis in mice [3].
• Binding of lipopolysaccharide (LPS) to membrane bound CD14 causes release of tumor necrosis factor-alpha and sepsis [4].
• Bovine CD14 receptor produced in plants reduces severity of intramammary bacterial infection [5].

High impact information on CD14

• Surface molecules attributed to myeloid cells, such as CD14, CD68, and scavenger receptor-1, were identified in both populations [6].
• Ethanol treatment resulted in steatosis, inflammatory infiltrates, occasional foci of necrosis, and elevated ALT in the absence of increased expression of the endotoxin receptor CD 14, a marker of Kupffer cell activation by LPS [7].
• For the first time, Toll-like receptor 4 mRNA and CD14 mRNA and protein were detected in bovine endometrial stromal and epithelial cells by RT-PCR and flow cytometry [1].
• The stimulatory effect of LPS plus fraction 2 serum proteins was dependent on the CD14 receptor, as monoclonal antibodies directed against CD14 (My4, 60bd; 10 micrograms/ml) inhibited tissue factor expression and TNF-alpha secretion by the macrophages [8].
• Soluble CD14 binds and neutralizes lipopolysacharide (LPS) and causes local recruitment of PMN after binding of CD14-LPS complexes to mammary epithelial cells [9].

Biological context of CD14

• The identity of the deduced amino acid sequence of bovine CD14 was 61-73% to those of mouse, rabbit and human [10].
• Genomic DNA encoding bovine CD14 was isolated from a bovine (Holstein) genomic library [10].
• Apoptosis was blocked by a monoclonal antibody against CD14, suggesting that LPS triggers apoptosis via a soluble CD14 (sCD14) dependent mechanism [11].
• When thioglycollate-elicited mouse peritoneal macrophages were stimulated with a high dose of LPS (10 micrograms/ml) in both the presence and absence of fetal calf serum, a source of LPS binding protein (LBP) necessary for the binding of LPS to CD14, NO production was observed [12].
• Among mononuclear BALF-cell populations, the gamma/delta TCR-expressing cells showed a pronounced transient increase in proportion as well as in relative cell size 2 weeks post primary infection, whereas CD4-, CD8-, Ig- and CD14-expressing cells showed no significant differences related to the infection [13].

Anatomical context of CD14

• Our results demonstrate that release of CD14 from PMN suppresses secretion of IL-8, and may be an important regulatory mechanism for controlling excessive migration of PMN into the bovine mammary gland [2].
• Double-labelling experiments with monoclonal antibodies against RPV and the myeloid marker CD14 confirmed that the infected blood adherent cells were monocytes and macrophages [14].
• As detected by immunolocalization, macrophage-like cells of various sizes showed a response for the CD18 surface molecule of leukocytes, for the CD45 molecule related to hemopoietic progenitor cells, and for the CD14 molecule selectively expressed on cells of the monocyte-macrophage lineage [15].
• RESULTS: CD14 in Kupffer cells was increased approximately 2-fold, and then it decreased and returned to control levels [16].
• All monocytes lost the expression of CD14 (the LPS receptor) upon infection with sporozoites [17].

Associations of CD14 with chemical compounds

• Lipopolysaccharide induces apoptosis in a bovine endothelial cell line via a soluble CD14 dependent pathway [11].
• In this model, CD14 in Kupffer cells was increased significantly 4 weeks after ethanol [16].
• DMSO was also able to induce expression of CD14 monocyte marker in the 3D4/31 cell line maintained in FBS containing medium, as determined by FACS with monoclonal antibody CAM36A [18].
• CD14 glycoprotein expressed in vascular smooth muscle cells [19].
• Application of 'class-specific' protease inhibitors revealed that a thiol/cysteine was involved in the biochemical production of soluble CD14 fractions and that a metalloprotease enzymatically degraded soluble CD14 fragment [20].

Other interactions of CD14

• Changes in leukocyte subpopulations in the blood of the calves were detected both with routine haematological methods and by FCM using specific monoclonal antibodies directed against CD14, CD45, CD2, CD4, CD8 and WC4 (a specific surface marker for bovine B-lymphocytes) [21].
• Short-term effects on pro-inflammatory cytokine, lactoferrin and CD14 mRNA expression levels in bovine immunoseparated milk and blood cells treated by LPS [22].

Analytical, diagnostic and therapeutic context of CD14

• The use of real time polymerase chain reaction showed that CD14 mRNA expression was not different between control and LPS-stimulated cells, indicating that the sCD14 came from either membrane bound CD14 or a preformed pool [2].
• Molecular cloning of bovine CD14 gene [10].
• Culture supernatant from 125I-surface-labeled bAM was examined for the existence of bovine CD14 using SDS-PAGE and autoradiography [23].
• Western blots probed with CD14-specific antibodies demonstrated that crude plant extracts and affinity-purified samples contained immunoreactive sCD14 [5].

References