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Biomedical subjects

M Zembala

Publications and source records attributed to M Zembala.

At least 163 records · Page 9Linked to original sources

The Fc receptors of normal and cancer patients monocytes.

The ability of human monocytes from normal donors and gastric-cancer patients to form rosettes with "O" Rh+(D) human erythrocytes coated with hyperimmune IgG anti-D antibody (EAhu) and to kill the same target in antibody-dependent cellular cytotoxicity (ADCC) were assessed. Trypsin pretreatment of normal monocytes decreased their ability to form rosettes with EAhu complexes, but their ADCC activity was unaffected. The Fc receptor (FcR) expression and ADCC activity of monocytes of cancer patients were elevated, and trypsin-treatment led to their further increase. The elevated values were related to the presence of the tumour. These results may suggest that human monocytes possess trypsin-sensitive and trypsin-resistant Fc receptors. The trypsin-resistant FcR seems to be involved in ADCC phenomenon and to be preferentially expressed on monocytes of some cancer patients.

Adult↗

Isolation of human monocytes by rosetting with antibody coated human erythrocytes and isopycnic gradient centrifugation.

Human erythrocytes O,Rh+ (D) coated with hyperimmune human anti-serum formed rosettes primarily with monocytes in peripheral blood mononuclear cell suspensions. The rosetting cells (EAhu-FRC), separated on a Lymphoprep gradient were found in the pellet and were up to 95% pure monocytes as judged by cytochemical criteria. A two step procedure involving depletion of T lymphocytes followed by the isolation of EAhu-RFC yielded monocytes up to 98% pure. The isolated cells did not respond to mitogens in vitro, but they act as accessory cells in mitogen-induced T lymphocyte proliferation. This simple method may be useful in studying monocyte function in human disease as it does not require a large amount of blood.

Adult↗

Inhibition of contact sensitivity by macrophages.

Lymphoid cells of mice injected with picrylsulphonic acid and then painted with picryl chloride produce a specific T suppressor factor (TSF) in vitro. This factor arms peritoneal exudate cells, which then produce a nonspecific factor which inhibits the transfer of contact sensitivity by immune cells incubated in it. An adherent, theta-negative cell, which is presumably a macrophage, is responsible. This justifies the use of the term macrophage suppressor factor. As a separate phenomenon, passive transfer cells lose their activity when incubated on high density monolayers of normal peritoneal exudate cells. However, this is not associated with the production of a supernatant factor. The inhibition of transfer when immune cells are incubated with specific TSF is unaffected by nylon wool filtration (which removes macrophages). This suggests that TSF is able to depress the passive transfer of contact sensitivity by a macrophage-independent process.

Animals↗

T suppressor cells and suppressor factor which act at the efferent stage of the contact sensitivity skin reaction: their production by mice injected with water-soluble, chemically reactive derivatives of oxazolone and picryl chloride.

The water soluble, chemically reactive thioglycollic acid thioether derivatives of oxazolone and picryl chloride were synthesized and tested for their ability to prevent the development of contact sensitivity. Mice given two injections of these agents showed partial or complete unresponsiveness when subsequently sensitized and challenged with oxazolone and picryl chloride, respectively. This unresponsiveness was associated with T suppressor cells, Ts-eff(cs), which blocked the efferent stage of the contact sensitivity reaction, i.e. the passive transfer of contact sensitivity. These Ts-eff(cs) were entirely specific when tested with the corresponding antigen. However, the suppression which they caused had a non-specific final common pathway. Cell from mice injected with the oxazolone and picryl thioethers and painted with the corresponding contact sensitizer produced a suppressor factor in vitro. This factor specifically blocked passive transfer by immune cells incubated in it. It also armed macrophages which then caused suppression. These macrophages were most effective when injected intraperitoneally. The suppressor factor had a molecular weight between 30,000 and 100,000 and the alpha-oxazolone factor was absorbed by oxazolone-albumin Sepharose and could be eluted with oxazolone-epsilon-aminocaproic acid. It was also absorbed by concanavalin-A-sepharose and could be eluted with alpha-methylmannoside. It is proposed that the ability of water soluble, chemically reactive haptenes to evoke a Ts-eff(cs) population may be relevent to the rarity of severe drug reactions following the injection of chemically reactive drugs.

Absorption↗

Inhibitory factor(s) of lymphoproliferation produced by synovial fluid mononuclear cells from rheumatoid arthritis patients: the role of monocytes in suppression.

Synovial fluid (SF) and synovial fluid mononuclear cells (SFM) were obtained from patients with rheumatoid arthritis (R.A.). The SF stimulated normal blood monocytes for nitroblue tetrazolium (NBT) reduction and inhibited normal lymphocyte response to PHA. Similar activities were found in supernatants from the cultures of SFM cells. Molecular weight of the lymphocytes inhibitory factor(s) produced by SFM was in range 50,000 to 100,000. The factor exerted its inhibitory activity via monocytes and had no direct toxic or blocking effect on lymphocytes. Monocytes played an active role in suppression presumably via production of a second-step inhibitory signal(s). It is suggested that the monocytes activated by the SFM-produced factor(s) are in turn triggered on for suppression of lymphoproliferation. These studies implicate that the state of monocyte activation is important in the regulation of lymphocyte responsiveness. This model of suppression may provide some explanation for SF lymphocyte hyporeactivity to mitogens in R.A.

Arthritis, Rheumatoid↗

Activation of human monocytes for nitroblue tetrazolium reduction and the suppression of lymphocyte response to mitogens.

Human peripheral blood mononuclear cells freed from polymorphs reduce nitroblue tetrazolium (NBT). This reduction is due to monocytes, i.e. adherent, phagocytic, esterase-positive cells with Fc receptors. Monocytes allowed to phagocytose zymosan show increased NBT reduction which under optimal conditions is 12.2 +/- 2.4 x 10(-9) mol . hr-1 . 10(-6) monocytes. Monocytes which have phagocytosed zymosan depress the mitogen response of human lymphocytes to PHA. This effect of 'activated' monocytes is due to a soluble inhibitory mediator which appears in the supernatant after culture for 24 hr. Its appearance requires protein synthesis. It is suggested that NBT reduction of peripheral blood mononuclear cells can be used as a test for the state of monocyte activation in disease. The possibility that activated monocytes may depress blast transformation in vitro in disease states is discussed.

Cell Adhesion↗

Mononuclear cell migration inhibition in children with nephrotic syndrome.

The relative number of T/B lymphocytes and the response of peripheral blood mononuclear cells to PHA in the migration inhibition test was studied in a group of patients with idiopathic nephrotic syndrome. It has been found that the level of T lymphocytes and the response to PHA was decreased in patients in particular those with frequent relapses. The possible implications of these finding for pathogenesis of idiopathic nephrotic syndrome is briefly discussed.

B-Lymphocytes↗

Intermediary role of macrophages in the passage of suppressor signals between T-cell subsets.

We have examined the ability of macrophages (Mphi) to transmit T-cell derived suppressor signals to other T cells. The suppressor signal studied is an antigen-specific factor which suppresses the ability of adoptively transferred, sensitized lymphocytes to express contact hypersensitivity in normal recipients. We have found that this factor binds to peritoneal exudate Mphi via cell surface structures which can be blocked with heat-aggregated gamma globulin. Dead (HK) Mphi bind the factor but fail to present it in a functional way to assay (immune) T cells, whereas live (L) Mphi perform both functions. Further, L Mphi can retrieve the factor in an active form from the surfaces of HK Mphi. Based on these and other findings (1-5), we discuss the possibility that Mphi may play as important a role in presenting T-cell communication signals to the cells of the immune system as they do in presenting antigen.

Animals↗