High FCR Research Articles

IFN-gamma plus glucocorticoids stimulate the expression of a newly identified human mononuclear phagocyte-specific antigen.

Glucocorticoid hormones, although able to exert profound immunosuppressive effects, do not suppress mononuclear phagocyte activation by IFN-gamma and may even enhance it. For example, expression and functional activity of the high affinity FcR for IgG on human mononuclear phagocytes (FcR gamma I) is increased by IFN-gamma and is maximal after co-treatment with IFN-gamma plus the glucocorticoid dexamethasone (DEX). To determine whether there are other mononuclear phagocyte surface Ag that are regulated in this manner, hybridomas were prepared using IFN-gamma-plus-DEX-treated human monocytes as immunogen. Five IgG1 mAb (Mac 2-8, 2-38, 2-48, 2-49, and 2-158) were developed that recognize a trypsin-sensitive mononuclear phagocyte-specific surface Ag of Mr 155,000. There was no detectable reactivity of these mAb to lymphocytes or granulocytes or to several cell lines, including U-937 and HL-60. The p155 Ag was detected on monocytes and increased significantly with time of culture or after treatment with DEX. Expression was maximal after co-treatment with rIFN-gamma plus DEX, but was inhibited or unaffected by treatment with IFN-gamma alone. For freshly isolated cells, expression of the p155 Ag was highest on peritoneal macrophages. Our results indicate that the p155 Ag is a newly identified Ag of the human mononuclear phagocyte lineage and may represent, in the least, a phenotypic marker of monocyte differentiation or maturation.

Normocholesterolemic tendon xanthomatosis with overproduction of apolipoprotein B

This report describes a 46-yr-old man with normocholesterolemic tendon xanthomatosis. He had severe bilateral xanthomas of Achilles tendons and small lesions on patellar tendons; biopsy of the latter revealed a fibroxanthoma of high cholesterol content. He did not have clinical evidence of atherosclerotic disease. The patient's total cholesterol (TC) and triglycerides (TG) were 245 and 258 mg/dl, respectively. LDL-TC was 168 mg/dl and HDL-TC was 32 mg/dl. VLDL consisted mainly of small particles (S f o 20–100) which were unusually rich in apolipoproteins B and E (and low in apo Cs). Plasma LDL-apo B was not increased (85–120 mg/dl), but VLDL-apo B was distinctly elevated (58 mg/dl). The synthesis rate of apoLDL (29.9 mg/kg/d) was increased markedly compared to a matched control (13.9 mg/kg/d) and to a patient with familial hypercholestrolemia (15.9 mg/kg/d). The concentration of apoLDL in our patient was not increased; this was because of an associated high FCR (0.484 day −1). His HDL was relatively low in TC but high in TG, which caused an increase in HDL 2b. The patient's xanthomata may have been the result of an overproduction of apo B possibly combined with a defect in HDL metabolism.

In Situ Fc Receptor-Bearing Cells in Two Murine Tumors. II. Role in Tumor Immunityo 2 o 3

The functional role of cells bearing Fc receptors (FcR's) in 2 murine tumors was investigated. Host-derived inflammatory cells were isolated from sarcomas induced in inbred C57BL/6 mice by murine sarcoma virus (MuSV) and from T1699 mammary adenocarcinomas in inbred DBA/2 mice. FcR-positive and FcR-negative cell populations were isolated by rosette formation with antibody-sensitized sheep red blood cells (SRBC's) followed by velocity sedimentation separation. The use of various antibody concentrations for SRBC sensitization allowed separation of different mononuclear cell populatlons by their FcR-binding characteristics. Cytotoxic T-cells within the MuSV-induced sarcomas did not have detectable levels of FcR. Growth-inhibitory cells in the sarcoma were, in large part, FcR-positive macrophages. In the T1699 mammary adenocarcinoma, the specific growth-inhibitory effector cells found within the tumor had high FcR activity characteristic of the monocytic cell series. An additional cell population capable of mediating antibody-dependent cytotoxicity was also isolated; these cells were weakly positive for FcR. Two populations of cell types capable of passively transferring delayed hypersensitivity (OHS) were isolated from the tumor: 1) a minor population, FcR-positive but θ-antigen-negative and 2) a larger population, θ-antigen-positive but FcR-negative. The results indicate that FcR-positlve cells may have several different and important functions in tumors and that FcR-binding properties may be used to identify and isolate specific effector cell populations. With the use of antibody-coated SRBC rosette formation as the probe, most FcR-positive effector cells involved in antitumor immunity appeared to belong to the monocytic cell series. Thymus-derived cytotoxic or DHS effector cells appeared to have low or undetectable levels of FcR.