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Biomedical subjects

R Gallily

Publications and source records attributed to R Gallily.

At least 19 recordsLinked to original sources

Phagocyte functions in familial Mediterranean fever.

Monocytes derived from peripheral blood of patients with familial Mediterranean fever (F.M.F.) demonstrated lower phagocytic capacity for Shigella flexneri and depressed bactericidal activity against S. albus when compared to monocytes from healthy individuals. Treatment of patients with colchicine did not alter these functions. On the other hand, chemokinesis of PMN of F.M.F. patients was enhanced especially during attacks. Colchicine treatment decreased significantly the PMN chemotactic migration.

Adolescent

Monocyte function in psoriasis.

Monocytes derived from the peripheral blood of psoriatic patients demonstrated a significantly higher phagocytic capacity (36 to 40%) for both 125I-labeled Shigella flexneri and 125I-labeled Staphylococcus albus compared with monocytes from healthy subjects. Monocytes from psoriatic patients showed a 2-to-4fold increase in bactericidal capacity against S. albus when compared with normal monocytes. However, the bactericidal capacity of monocytes from diphylline-treated patients did not differ from that of the control subjects. The antibody-dependent cellular cytotoxicity (ADCC) activity against EL4 tumor cells was found to be similar in both psoriatic patients and control subjects. It is postulated that these abnormalities of monocyte function in psoriasis are caused by a decreased cAMP/cGMP ratio similar to the decreased cAMP/cGMP ratio found in the lesional epidermis of this disease. It seems therefore, that the psoriatic abnormality is not confined to only one type of cell, the epidermal cell.

Adult

Macrophage fatty acid composition and phagocytosis: effect of unsaturation on cellular phagocytic activity.

In order to manipulate the physical properties of the macrophages membrane, methods were developed which potentiated the incorporation of exogenously supplied fatty acids into membrane lipids. Chromatograms of macrophages which were grown in the presence of a variety of fatty acids demonstrated that exogenously supplied unsaturated fatty acids (palmitoleic, oleic, elaidic, linoleic, linolenic and arachidonic acids) were readily incorporated into the cells and selectively altered the fatty acyl composition of macrophage phospholipids. Up to 38% of the total cellular phospholipids were found to be derived from the exogenously added fatty acid supplements. The incorporation of the different fatty acids into cellular phospholipids had striking effects on cellular phagocytic activity. These effects were found to correlate with the degree of unsaturation, and the cis- or trans-double bond configuration. Thus, macrophage phagocytic ingestion rates of 125I-labelled Shigella flexneri were found to alter by more than 2-fold after the cells were cultivated in the presence of cis unsaturated fatty acids.

Animals

Enhanced chemotactic and phagocytic activities of leukocytes in psoriasis vulgaris.

Leukocytes derived from the peripheral blood of psoriatic patients demonstrated an enhanced chemotactic response compared with leukocytes from healthy subjects. No significant difference was detected between the chemotactic response of leukocytes from patients with minimal or no skin involvement and those from patients with extensive lesions. Psoriatic leukocytes also had a significantly higher capacity to engulf 125I labeled Shigella flexneri than control leukocytes. It is postulated that a decrease in the cyclic AMP/cyclic GMP ratio in psoriatic leukocytes, similar to the imbalance of these 2 cyclic nucleotides found in the lesional epidermis of psoriasis, might be the cause of their enhanced chemotactic and phagocytic activities.

Cyclic AMP

The mode of interaction with macrophages of two ordered synthetic polypeptides which differ in their thymus dependency.

The mode of interaction with macrophages of two ordered synthetic polypeptides (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys), (T-T-G-G)-A--L, and (Tyr-Glu-Tyr-Glu)-poly(DLAla)--poly(Lys), (T-G-T-G)-A--L, which differ in their requirements for T-B cell co-operation in the process of antibody production, was compared. The binding of the two radiolabelled antigens to the surface of peritoneal adherent cells, their uptake by the cells and the rate of their degradation were investigated. Macrophages were found to be capable of degrading both poly-peptides with the same efficiency. (T-G-T-G)-A--L, the antigen which is less T-dependent, was bound to macrophage surfaces more readily than (T-T-G-G)-A--L, the T-dependent antigen, however, its uptake by the cells was found to be lower. Thus, (T-G-T-G)-A--L remains for a longer period in the form of a membrane bound polyvalent antigen.

Animals

Quantitative in vitro phagocytic rate measurements.

A model for the calculation of phagocytic rate constants based on the assumption that the process of phagocytosis can be treated in a manner analogous to chemical reactions of the first order is suggested. By employing such an approach, accurate rate constants of ingestion of in vitro cultivated macrophages can be obtained following minimal time intervals from the onset of phagocytosis.

Animals

Potentiation of mouse peritoneal macrophage antibacterial functions by treatment of the donor animals with the methanol extraction residue fraction of tubercle bacilli.

Administration to inbred mice of the methanol extraction residue fraction of tubercle bacilli by some, but not by all, routes affected markedly the in vitro phagocytic and antibacterial capacities of their peritoneal macrophages harvested several days to weeks after treatment. Phagocytosis of living [3H]thymidine- labeled Staphylococcus albus and Staphylococcus aureus organisms, but not of Listeria monocytogenes, was markedly enhanced. Uptake of the deoxyribonucleic acid precursor thymidine by the phagocytized staphylococci was consistently and significantly inhibited in macrophages taken from methanol extraction residue-treated donors. Such macrophages also displayed a significant facility to reduce the viability of intracellular S. albus and L. monocytogenes, but not of S. aureus, under the present experimental conditions.

Animals

Macrophage phagocytic recognition sites. Demonstration of selectivity by hetero- and alloantisera.

Separate and independent phagocytic recognition sites have been identified on mouse peritoneal macrophages through the use of xenogeneic antimacrophage serum (AMS) and allogeneic anti H-2 antisera. Anti H-2d and anti H-2b antisera inhibit the binding and ingestion of opsonized erythrocytes (EA) by macrophages bearing H-2 haplotypes d and b, respectively. AMS and its F(ab')2 and Fab fragments inhibit the binding and ingestion of EA, and the ingestion but not the binding of 125I-labelled Shigella by macrophages. Neither antiserum inhibited the binding or ingestion of latex particles by macrophages. The results suggest that particulate binding to macrophages can be inhibited by two different mechanisms: a non-specific one where antibody bound to certain cell-surface antigens can mediate either directly or indirectly, and a specific interaction with Fc receptors. The possible mechanisms of non-specific antibody mediated phagocytic inhibition are discussed.

Animals

Motion of spin-labeled fatty acids in murine macrophages. Relation to cellular phagocytic activity.

Macrophage membrane fluidity was investigated with respect to cellular phagocytic activity through the use of fatty acid spin labels. Spin-labeled fatty acid derivatives were incorporated into intact mouse peritoneal macrophages by exchange from bovine serum albumin. The electron spin resonance (ESR) spectra of the spin-labeled fatty acids in the macrophages showed a pronounced temperature dependence and a decrease in the hyperfine splittings (2 T11) of the spectra as the nitroxide radical was moved away from the polar head group of the fatty acid derivatives. Spin-labeled macrophages underwent a time- and temperature-dependent decay, which was inhibited by preincubating the cells with mercuric chloride, heating at 56 degrees C, or by fixing them with 0.25% glutaraldehyde. No correlation between the phagocytic activity of macrophages and membrane freedom of motion could be demonstrated. Treatment of macrophages with anti-macrophage serum or extended in vitro cultivation inhibited cellular phagocytic activity but exerted no effect on the motional freedom of the macrophage membrane. Enrichment of the fatty acid composition of the macrophage membrane with cis- or trans-unsaturated fatty acids had striking effects on cellular phagocytic activity, while no significant changes could be detected in the freedom of motion of incorporated fatty acid spin labels at the degree of specific enrichment achieved here. Thus no correlation between cellular phagocytic activity and lipid motion could be detected.

Animals

Studies on the relationships between the immunogenicity and catabolism of antigens and their binding to the surface of macrophages.

The relationship between immunogenicity of Shigella paradysenteriae, the branched synthetic polypeptide poly-L (Tyr, Glu)-polylpro-polyllys [(T, G)-Pro--L] and human albumin (HSA) interacting with macrophages and kinetics of antigen degradation and degree of binding to the cell surface was studied. Following thioglycollate inoculation into C57BL/6 mice, the peritoneal-stimllated macrophages had higher levels of hydrolases as compared to unstimulated cells. The lysates of the stimulated macrophages catabolized the three labeled antigens faster than did the lysates of unstimulatec cells. However, when degradation of labeled antigens by macrophage cells was assessed, no direct correlation could be demonstrated between the level of cell hydrolases and rate of (T, G)-Pro--L or HSA catabolism. The immunogenicity of antigens following their uptake by unstimulated and stimulated macrophages was determined by transfer of the antigen-bearing cells into irradiated and nonirradiated syngeneic recipients. No correlation was apparent between the rate of antigen degradation and the capacity to evoke a humoral response. Similarly, no correlation could be demonstrated between the amount of antigen bound to the macrophage cell surface and the immunogenicity of the antigen. It is suggested that neither the rate of antigen catabolism by macrophages nor the amount of antigen bound to the macrophage membrane is the sole factor which determines the immunogenicity of antigens interacting with macrophages.

Animals

Macrophage killing capacity. Aspects of mechanism.

Immune macrophages have the capacity to kill in mixed macrophage cultures (MMC) allogeneic macrophages bearing the alloantigens used for immunization. The killing is expressed by a lytic mechanism as neither phagocytosis nor fusion between effector and target cells could be detected by E.M. T but not B lymphocytes isolated from immune spleen cells, are able to "arm" syngeneic nonimmune macrophages and render them cytotoxic. It is suggested that mediator(s) and/or membranal components are released from T cells and attach to macrophages. Such an "arming" factor enables the macrophage to recognize and kill target cells.

Animals