The CD14 differentiation antigen mediates the development of endotoxin responsiveness during differentiation of mononuclear phagocytes

Abstract

The CD14 antigen was originally described as a differentiation antigen on mononuclear cells. The purpose of this study was to investigate the relationship between the appearance of surface CD14 and the acquisition of lipopolysaccharide (LPS) responsiveness during maturation of mononuclear phagocytes. Immature THP-1 cells responded poorly to LPS in the absence or presence of serum. Treatment with the maturational agent calcitriol caused a dose- and time-dependent increase in CD14 mRNA and surface CD14 and enhanced the responsiveness of THP-1 cells to smooth and rough form LPS, complexes of LPS and lipopolysaccharide-binding protein (LBP), and LPS in low concentrations of serum. Monoclonal antibodies to CD14 blocked the responses of THP-1 to LPS, LPS-LBP complexes and LPS in serum. Immunodepletion of LBP from serum also inhibited the effect of LPS in serum. The data show that maturation of the response of THP-1 cells to LPS and LPS-LBP complexes depends on the appearance of CD14 on the cell surface. Maturation of the response to LPS in serum depends in large part on the appearance of CD14 on the cell surface and the presence of LBP in serum.

Toll-Like Receptor (TLR)2 and TLR4 in Human Peripheral Blood Granulocytes: A Critical Role for Monocytes in Leukocyte Lipopolysaccharide Responses

“…At the protein level, basophils did not express all the components of the LPS receptor, because they expressed TLR2 and TLR4 at levels similar to or greater than those in neutrophils, but not CD14. However, lack of membrane CD14 is not necessarily a bar to LPS responsiveness (58), and soluble CD14 is present in FCS as used in all our assays (59), which has been shown to enable LPS responses in some, but not all, CD14-negative cells (60,61). Soluble CD14 is effectively delivered to sites of allergic inflammation (62), and the presence of TLR2 and TLR4 on the basophil suggests that LPS responsiveness in this cell type may be inducible at sites of inflammation.…”

Differential Regulation of Membrane CD14 Expression and Endotoxin-Tolerance in Alveolar Macrophages

“…Numerous studies have demonstrated that mCD14, which belongs to the family of GPIanchored glycoproteins, can be released from cells by treatment with PI-PLC (11,36). However, it also has been reported that protease-dependent shedding causes downregulation of mCD14 on PMA-stimulated monocytes (29).…”

“…CD14, the receptor for LPS, is implicated in various immune responses including activation of the innate immune system (6), bacterial phagocytosis (7), and clearance of apoptotic cells (8). Macrophages recognize LPS via membrane CD14 (mCD14) and toll-like receptor-4 (TLR4), a member of the toll-like receptor family which mediate signaling in response to a number of microbial components (9)(10)(11). Recognition of LPS by the CD14/TLR4/MD-2 complex activates intracellular signaling pathways involving mitogen-activated protein (MAP) kinases, resulting in the production of proinflammatory cytokines and chemokines (12)(13)(14).…”

Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44.

“…We sought to determine if CD14, the LPS receptor, was involved in mediating the HA effect since LPS is capable of inducing all of the chemokine genes studied here. CD14 was originally described as a differentiation antigen on monocytes, but it has since been recognized as the receptor for the complex of LPS with lipopolysaccharide binding protein (54,55). The human monocytic leukemia cell line THP-1 possesses CD44 but expresses essentially no CD14 as demonstrated by flow cytometry in Fig.…”