Distribution and comparison of receptors for leukemia inhibitory factor on murine hemopoietic and hepatic cells

Abstract

Leukemia inhibitory factor (LIF) is a glycoprotein that induces the differentiation of the monocytic leukemia cell line M1 but suppresses the differentiation of totipotent embryonic stem cells. In an attempt to define the normal cellular targets for LIF, the distribution of LIF receptors within hemopoietic and hepatic tissue was analyzed by binding cells with radioiodinated LIF (125I-LIF) and subsequently carrying out autoradiography. Autoradiography demonstrated that in each hemopoietic tissue examined cells of monocyte/macrophage lineage were the primary cell type labeled with 125I-LIF. Moreover, both fetal and adult parenchymal hepatocytes displayed higher levels of labeling than either monocytes or macrophages. The number of receptors per positive cell varied from 150 for bone marrow monocytes to 2,000 for adult hepatocytes. In each case, however, binding was of high affinity, with an apparent KD of 34-100 pM, and binding was specific, since labeling was competed for by unlabeled LIF but not a range of other structurally unrelated growth and differentiation factors. It is suggested that LIF may play a role in regulating macrophage function and hepatic acute phase protein synthesis in response to infection.

Continued Administration of Ciliary Neurotrophic Factor Protects Mice from Inflammatory Pathology in Experimental Autoimmune Encephalomyelitis

“…41,61 The effect of CNTF on spinal cord inflammation is unlikely to be linked to a direct effect of this cytokine on T cells because these cells are neither known to express CNTFR␣ nor LIFR␤. 13,65,66 It is conceivable that CNTF exerts its effects on the spinal cord immune response via immune modulating molecules produced by microglia, a cell population known to respond to CNTF 67,68 or a direct neuroprotective effect preventing initial myelin and axon damage and therefore blocking secondary inflammatory response. 69 The ability of CNTF to cross the BBB is prerequisite for a direct effect of CNTF on microglial cells or myelin and axons.…”

Expression and function of members of the cytokine receptor superfamily on breast cancer cells

“…The radioiodination of LIF and OSM and binding assays were essentially performed as previously described (Hilton et al, 1991;Hilton and Nicola, 1992). Brie¯y, 50 ml aliquots containing 1610 7 cells, suspended in RPMI-1640 medium containing 10% BCS, were placed in Falcon tubes with 40 ml of the respective radioiodinated ligand at 1610 5 c.p.m.…”

Analysis of Intracellular Signaling Kinetics Predicts Presentation Modes and Targets for Stem Cell Fate Control

“…The Matlab software package (The Mathworks, http://mathworks.com) was used for model development and implementation. Signal propagation starts with binding of LIF to its LIFR [10,11]; this is followed by recruitment of the glycoprotein 130 (GP130) receptor to form a stabilized heterodimeric receptor complex on the cell surface. Transient homodimers of LIFR and GP130 are nonsignaling in this system [12].…”

“…This is the suggested mode of action of SHP2 in this system [21,[24][25][26]. Trafficking of the receptors GP130 and LIFR is also implemented in the model, and all surface receptors can be internalized with the same rate constant (K28), there is a fixed rate of receptor production using rate constant K29, and internalized complexes do not signal and are degraded [11,28,29]. Using this system, we are able to capture the observed transient kinetics of the Jak/Stat3 pathway.…”

“…In mouse ESCs, Stat3 activation results from binding of leukemia inhibitor factor (LIF) to the LIF receptor and glycoprotein-130 (GP130), forming a heterodimeric receptor complex [10,11]. Jakmediated Src homology-2 (SH2)-domain phosphorylation of receptors leads to Stat3 recruitment to the receptor complex [12], and its Tyr-705 phosphorylation and subsequent nuclear accumulation [13][14][15][16][17][18][19][20][21][22][23][24][25].…”