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Biomedical subjects

D H Boldt

Publications and source records attributed to D H Boldt.

At least 55 records · Page 3Linked to original sources
PubMed1986

Phorbol diesters and transferrin modulate lymphoblastoid cell transferrin receptor expression by two different mechanisms.

Expression of transferrin receptors (TfR) by activated lymphocytes is necessary for lymphocyte DNA synthesis and proliferation. Regulation of TfR expression, therefore, is a mechanism by which the lymphocyte's proliferative potential may be directed and controlled. We studied mechanisms by which lymphoblastoid cells modulate TfR expression during treatment with phorbol diesters or iron transferrin (FeTf), agents which cause downregulation of cell surface TfR. Phorbol diester-induced TfR downregulation occurred rapidly, being detectable at 2 min and reaching maximal decreases of 50% by 15 min. It was inhibited by cold but not by agents that destabilize cytoskeletal elements. Furthermore, this downregulation was reversed rapidly by washing or by treatment with the membrane interactive agent, chlorpromazine. In contrast, FeTf-induced TfR downregulation occurred slowly. Decreased expression of TfR was detectable only after 15 min and maximal downregulation was achieved after 60 min. Although FeTf-induced downregulation also was inhibited by cold, it was inhibited in addition by a group of microtubule destabilizing agents (colchicine, vinblastine, podophyllotoxin) or cytochalasin B, a microfilament inhibitor. Furthermore, FeTf-induced downregulation was not reversed readily by washing or by treatment with chlorpromazine. The inactive colchicine analogues, beta- and gamma-lumicolchicine, did not inhibit FeTf-induced TfR downregulation. Similarly, when cells were pretreated with taxol to stabilize microtubules, colchicine no longer inhibited FeTf-induced downregulation. Therefore, FeTf causes TfR downregulation in lymphoblastoid cells by a cytoskeleton-dependent mechanism. Phorbol diesters cause TfR downregulation by a cytoskeleton-independent mechanism. In other experiments, treatment of cells with both a phorbol diester and FeTf, either simultaneously or sequentially, produced additive effects on TfR expression. These data indicate that TfR expression is regulated by two independent mechanisms in lymphoblastoid cells, and they provide the possibility that downregulation of TfR by different mechanisms may result in different effects in these cells.

Cell Line↗
PubMed1985

Binding of isolectins from red kidney bean (Phaseolus vulgaris) to purified rat brush-border membranes.

Ingestion of red kidney bean phytohemagglutinin causes impaired growth and intestinal malabsorption, and facilitates bacterial colonization in the small intestine of weanling rats. We have studied interactions of the highly purified phytohemagglutinin erythroagglutinating (E4) and mitogenic (L4) isolectins with microvillous membrane vesicles prepared from rat small intestines. E4 and L4 were radioiodinated with 125I by the chloramine-T technique. E4 and L4 isolectins both bound to microvillous membrane vesicles. Binding was saturable and reversible. Each mg of membrane protein bound 744 +/- 86 micrograms E4 and 213 +/- 21 micrograms L4. The apparent Ka for E4 and L4 binding was 2.5 x 10(-6) and 13.0 x 10(-6) M-1, respectively. Binding of each 125I-labelled isolectin was abolished by 100-fold excess of unlabelled isolectin. In each case binding also was inhibited by appropriate oligosaccharide inhibitors, indicating that isolectin-microvillous membrane interactions were mediated by carbohydrate recognition. Patterns of saccharide inhibition of isolectin binding were different for E4 and L4. Competitive binding experiments demonstrated mutual noncompetitive inhibition of E4 and L4 binding consistent with steric hindrance. Therefore, E4 and L4 each bound to its own set of receptors. Based on the known saccharide specificities of E4 and L4, these data indicate that there are differences in expression of complex asparagine-linked biantennary and tri- or tetraantennary oligosaccharides at the microvillous surface. The data also provide the possibility that direct interactions of one or more phytohemagglutinin isolectins with intestinal mucosa in vivo may contribute to the antinutritional effects associated with ingestion of crude red kidney beans.

Animals↗
PubMed1985

Phase I evaluation and pharmacokinetics of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193).

Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, TCAR, Riboxamide, NSC 286193) is a novel C-nucleoside with antitumor activity against several murine tumor models, including Lewis lung carcinoma. The mechanism whereby this compound exerts its antineoplastic effects is most likely related to a state of guanine nucleotide depletion whereby the anabolite, thiazole-4-carboxamide adenine dinucleotide, potently inhibits inosine-5'-monophosphate dehydrogenase. This Phase I study was designed to determine the maximally tolerated dose of Tiazofurin administered on a 5-day, every-28-day schedule. Tiazofurin levels were measured using a high-pressure liquid chromatography assay, and pharmacokinetic studies were performed in patients treated at each dose level. Nineteen patients received a total of 24 courses of the drug in doses ranging from 550 to 2200 mg/sq m. The dose-limiting toxicities were pleuropericarditis and a general illness best described as a "viral-like" syndrome (manifested by severe malaise, headaches, myalgias, fever, nausea, vomiting, and diarrhea). Other toxicity included myelosuppression, hyperuricemia, elevated serum creatine phosphokinase and serum glutamic oxaloacetic transaminase, conjunctivitis, mucositis, and desquamation of the palms of the hands. Plasma clearance of Tiazofurin followed a biexponential pattern with a harmonic mean terminal half-life of 7.6 h. The mean volume of distribution at steady state was 30 liters/sq m, and the mean plasma clearance was 3 liters/h/sq m. The total cumulative urinary excretion ranged from 15 to 49%. The maximally tolerated dose of Tiazofurin on a 5-day schedule was 1650 mg/sq m. The recommended dose for Phase II evaluations is 1100 mg/sq m for 5 days. However, exploration of other schedules which might allow administration of more Tiazofurin combined with biochemical studies including thiazole-4-carboxamide adenine dinucleotide measurements would be desirable.

Adult↗
PubMed1984

Receptors for pea and lentil lectins on human lymphoid cells: demonstration of distinct lectin-defined cell subclasses.

Lectins are useful probes for studying cell surface glycoconjugates. Pea (PL) and lentil (LL) lectin each requires for binding a fucosyl- and two alpha-mannosyl residues in core regions of glycopeptides, but differences in outer chain carbohydrates may alter their relative binding affinities. We used binding studies with [125I]-PL and LL and flow cytometry with fluorescein-conjugated (FITC)-PL and -LL to study their interactions with peripheral lymphocytes. Binding of both lectins to lymphocytes was saturable, reversible, and inhibited by alpha-methyl mannose. Scatchard analyses were consistent with two classes of receptors for each lectin. Flow cytometric analyses demonstrated that cell to cell receptor densities varied. Sixty-five percent of lymphocytes bound PL (mean 2 X 10(6) receptors/cell) and 45% bound LL (mean 3 X 10(6) receptors/cell). Competition studies demonstrated mutual inhibition, but flow cytometry revealed persistent FITC-PL or -LL binding depsite 20-fold molar excess of the other lectin. Distributions of receptors for PL and LL on lymphocytes were as follows: 45% of lymphocytes bound both PL and LL; 20% of lymphocytes bound PL alone; 35% of lymphocytes bound neither PL nor LL. Despite similar binding requirements for PL and LL and overlap between their receptors on lymphocytes, there appear to be subsets of receptors specific for each lectin. These results may reflect abilities of PL and LL to discriminate subtle carbohydrate differences on lymphocyte surfaces.

Binding, Competitive↗
PubMed1984

Phytohemagglutinin-induced diarrheal disease.

A purified plant lectin, phytohemagglutinin (PHA), or crude red kidney bean (RKB) from which it was derived, when incorporated as 1% of dietary protein into a purified casein protein diet caused weanling rats to fail to grow or lose weight in comparison to control animals pair fed an isonitrogenous, isocaloric diet. Feeding PHA was observed to cause diarrhea: fecal wet and dry weights were increased within 2 days after starting the diet. Increased fecal weight was caused by increased dry weight as well as by an increased fecal water content. On reversion to a normal casein diet, rapid amelioration of the antinutritional effects of PHA occurred with resumption of normal growth rate. Specific binding of PHA to the microvillus region of the small intestinal epithelium was demonstrated using rabbit anti-PHA and fluorescein-labeled goat anti-rabbit immunoglobin. PHA binding was observed after chronic intake in the diet or when applied to normal tissue in vitro. Loss of PHA binding to the intestine was observed to occur within 48 hr on reversion to a control casein diet. No significant morphological damage to the microvilli or the mucosal villus architecture was observed to accompany PHA adherence under these experimental conditions. Antinutritional and antiabsorptive effects of dietary PHA were associated with diarrhea. PHA adhered to the microvillus membrane of the small intestinal villus surface during the diarrheal state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Wheat germ agglutinin decreases expression of the T8 antigen on human peripheral mononuclear cells.

We examined dynamics of expression of the human T-suppressor specific antigen, T8, following interaction of peripheral lymphocytes with wheat germ agglutinin (WGA). Cells were incubated at 37 degrees C with or without WGA (15 micrograms/ml) for 18 hrs, washed sequentially with N-acetylglucosamine (to remove bound WGA) and plain medium, then analyzed by flow cytometry for binding of lectins and monoclonal antibodies OKT8(T-suppressor specific) and OKT3 (pan-T specific). WGA pretreatment induced an overall 65% reduction in WGA binding and concomitant 30% reduction in percentage of T8+ cells. Furthermore, residual T8+ cells showed 50% reduction in T8 expression. Taking into account reductions in both percentages of T8+ cells and also antigen densities, WGA reduced T8 expression by greater than 60% overall. By contrast, binding of OKT3 and the lectins, concanavalin A (con A) and Ricinus communis agglutinin (RCA-I), was unaffected by WGA. The decreased T8 expression could not be explained by residual cell bound WGA and was fully reversible within 48 hours of removal of cells from WGA-containing medium. Therefore, WGA caused downregulation of T8 antigen expression. The effect of WGA was time- and concentration-dependent. Downregulation did not occur at 4 degrees C nor in the presence of azide, thereby demonstrating a requirement for cellular metabolism. The data suggest that WGA may bind to the T8 antigen, and they provide the possibility that similar downregulation of T8 by WGA may underlie certain of the in vitro immunoregulatory effects of this lectin.

Antibodies, Monoclonal↗
PubMed1984

Effects on human peripheral lymphocytes of in vivo administration of 9-beta-D-arabinofuranosyl-2-fluoroadenine-5'-monophosphate (NSC 312887), a new purine antimetabolite.

9-beta-D-Arabinofuranosyl-2-fluoroadenine-5'-monophosphate (NSC 312887) (2-F-ara-AMP) is a new purine antimetabolite with documented preclinical activity against a number of animal tumors. Data from in vitro studies and preclinical animal toxicology trials indicated that 2-F-ara-AMP might be lymphocytotoxic. We studied effects of 2-F-ara-AMP on peripheral lymphocytes of patients receiving the agent in a Phase I clinical trial. Eleven patients received 13 courses given by i.v. bolus daily for 5 days. Mononuclear cells were isolated, and lymphocyte subsets were quantitated by immunofluorescence and flow cytometry 1 day before treatment and 4 hr after the final infusion. Lymphocytopenia developed rapidly (median time to nadir, 6 days) and was reversible. Standard leukocyte counts, differential counts, and percentages of isolated mononuclear cells reactive with monoclonal antibodies were used to calculate numbers of peripheral cells in each major lymphocyte subpopulation. Total T-lymphocyte counts fell during all treatment courses, with calculated mean absolute T-cell counts decreasing by 90%. Decreases were observed in all major T-lymphocyte subsets. By contrast, calculated B-lymphocyte counts decreased an average of 50% and were noted to increase during two treatment cycles. We also compared in vitro recoveries of cells from each major lymphocyte subpopulation before and after administration of 2-F-ara-AMP. Recoveries of total mononuclear cells, total T-cells, and non-T-, non-B-cells all were reduced substantially by 2-F-ara-AMP, but B-cell recovery was not reduced. These in vivo data, the first in human subjects, are in agreement with in vitro studies of halopurine nucleotide analogues which have demonstrated that T-cells are more sensitive than are B-cells to the cytotoxic effects of these compounds.

Adult↗
PubMed1984

Perturbation by insulin of human breast cancer cell cycle kinetics.

The growth of cultured human breast cancer cells is sensitive to physiological concentrations of insulin suggesting that it may regulate breast cancer growth in vivo. The mechanisms for the growth effects of insulin are poorly defined. In the present study, we examine the effects of insulin on the cell cycle kinetics of asynchronous MCF-7 human breast cancer cells growing in serum-free medium. When the [3H]thymidine labeling index is used to estimate the S-phase fraction, insulin added to asynchronously growing cells results in a time-dependent increase in the proportion of cells engaged in DNA synthesis. Computer analysis of DNA histograms obtained by flow cytometry of mithramycin-stained cells also shows a time-dependent progression of cells into and through the S-phase compartment. Sixteen hr after adding insulin to asynchronous cells, 66% of cells are in S-phase compared to 37% in controls. The effect of insulin on the cell cycle progression of MCF-7 cells is also dose dependent. Stimulation is observed with physiological insulin concentrations of 0.1 to 1.0 nM; maximal effects are observed with 1.0 to 10 nM insulin. Various insulin analogues enhance the progression of cells into S phase in proportion to their ability to bind to the insulin receptor in MCF-7 cells (porcine greater than or equal to chicken greater than guinea pig greater than deoctapeptide insulin), while unrelated peptide hormones have no effect on the cell cycle kinetics. Cell cycle analysis after the addition of colchicine to prevent mitosis and the reentry of cells into G1 demonstrates a shortened G1 in response to insulin. Continuous [3H]thymidine-labeling studies after the addition of colchicine suggest that the growth fraction is about 88% with or without insulin. In summary, insulin causes a marked perturbation of the cell cycle kinetics of MCF-7 human breast cancer cells by facilitating the transit of cells through G1. The data also suggest that this effect is mediated via the insulin receptor.

Animals↗
PubMed1984

Human breast cancer cell cycle synchronization by estrogens and antiestrogens in culture.

The mechanisms by which estrogens and antiestrogens modulate breast cancer growth have not been totally defined. We have examined the cell cycle kinetic effects of estrogens and antiestrogens in cultured human breast cancer cell lines. In a previous study, we showed that tamoxifen induces a transition delay in early to mid-G1 phase of the cell cycle. In the present study, we show that this cell kinetic alteration by tamoxifen is dose dependent and that other antiestrogens have identical effects. As little as 0.01 to 0.1 microM tamoxifen reduces the S and G2 + M fractions and increases the G1 fraction of MCF-7 cells growing in medium with 5% charcoal-stripped bovine serum. More than 90% of cells are in G1 72 to 96 hr after the addition of 1 microM tamoxifen, a concentration achieved in patients treated with the drug. Nafoxidine and trioxifene have identical activity. Partial reversal of tamoxifen growth inhibition is observed with a simple change to tamoxifen-free medium. Complete reversal of the tamoxifen effect is observed with the addition of 17 beta-estradiol. By 24 hr after the addition of estrogen, 60 to 70% of tamoxifen-inhibited cells have progressed through G1 and into S phase, indicating that tamoxifen-treated cells remain viable. This estrogen "rescue" effect is observed even in the absence of a change to tamoxifen-free medium. A 100-fold-lower concentration of estradiol can totally reverse the inhibitory effects of 1.0 microM tamoxifen. Stimulation of the progression of G1 cells to enter S phase is also observed when estradiol is added to cells maintained for four days in medium with stripped serum, even in the absence of tamoxifen. Similar effects are observed in the estrogen receptor-positive ZR75-1 breast cancer cells. No effects of antiestrogens or estrogens are observed in the receptor-negative MDA-231 cells, suggesting that these effects are mediated through the estrogen receptor. In summary, antiestrogens and estrogens have prominent effects on the cell cycle kinetics of endocrine-dependent human breast cancer cells. Antiestrogens cause an accumulation of cells in G1 phase. Estrogen reverses this block with a synchronous cohort of cells progressing through the cell cycle. These data have important implications for the design of rational clinical trials of combined chemoendocrine therapy.

Breast Neoplasms↗
PubMed1983

Lymphocyte subpopulations in chronic lymphocytic leukemia detected by lectin binding and flow cytometry.

Flow cytometry was used to compare binding of wheat germ agglutinin (WGA) and Lens culinaris lectin (Lcl) to peripheral lymphocytes (PBL) from normal subjects and 26 patients with chronic lymphocytic leukemia (CLL). As defined by the interactions of WGA and Lcl with cell surface receptors, normal unfractionated PBL and purified B-cells were heterogeneous, containing subclasses that bound to WGA (WGA+Lcl-), Lcl (WGA-Lcl+), both (WGA+Lcl+), or neither (WGA-Lcl-). By contrast, in 25 of 26 CLL patients, PBL were homogeneous with approximately 90% of cells binding one or both lectins. Apparent monoclonal tumor cell populations were identified in these patients corresponding to the normal lectin defined cell subclasses: WGA-Lcl- in 18 patients; WGA-Lcl+ in four patients; WGA+Lcl+ in three patients. Ten patients were studied sequentially on more than one occasion at intervals of five to 15 months. Lectin binding patterns remained stable within this time frame. These findings demonstrate that lectin binding may detect several CLL subclasses corresponding to lectin-defined subsets of normal PBL. Lectins can serve as useful tools for dissecting the heterogeneity of human lymphoproliferative diseases.

Flow Cytometry↗
PubMed1983

Analysis of lectin receptors on rat embryo fibroblasts transformed by adenovirus 2.

Transformation of rat embryo fibroblasts by human adenovirus type 2 (Ad2) results in the production of a series of cell lines that cover a spectrum of malignancy from nontumorigenic to highly tumorigenic in a single species. A panel of plant lectins was used to study surface characteristics of these cell lines that might correlate with tumorigenicity. Because of the complex nature of lectin-cell surface interactions, a number of parameters were determined; they included numbers and densities of lectin receptors, binding affinities, and receptor mobilities. The lectins from Lens culinaris, Lotus tetragonolobus, and Ricinus communis were found to be the most useful for differentiating among the various Ad2-transformed cell lines. In general, the more tumorigenic cell lines were characterized by high numbers of lectin receptors, high percentages of lectin-binding cells, and heterogeneous distributions of receptors from cell to cell. In contrast, the nontumorigenic and the weakly tumorigenic cell lines were characterized by low numbers of lectin receptors present on a minority of cells within each population and a more homogeneous distribution of these receptors from cell to cell. These data demonstrate that lectins can identify surface properties that appear to correlate with malignant potential in the Ad2-transformed cell lines.

Adenoviruses, Human↗
PubMed1983

Interactions of lectins and monoclonal antibodies with human mononuclear cells. I. Specific inhibition of OKT4 and OKT8 binding by Ricinus communis agglutinin and wheat germ agglutinin.

We used flow cytometry to examine effects of lectins on interactions between human lymphocytes and the anti-T cell monoclonal reagents OKT4 (T helper-specific) and OKT8 (T suppressor-specific). Wheat germ agglutinin (WGA) inhibited OKT8 binding to lymphocytes by a mean 77% and Ricinus communis agglutinin (RCA-I) inhibited OKT4 binding by 66%. Inhibition was abolished in each case by appropriate carbohydrate hapten inhibitors of lectin binding, indicating it was mediated by the lectin saccharide combining sites. Neither WGA nor RCA-I inhibited binding of OKT3, a pan-T cell monoclonal reagent. In addition, a group of other lectins with a variety of nominal carbohydrate specificities did not inhibit OKT4 or OKT8 binding. Preincubation experiments and gel filtration indicated that inhibition in each case was due to competition between lectin and monoclonal for binding to cell surfaces, not to direct lectin-monoclonal antibody interactions. Treatment of lymphoid cells with OKT8 and complement reduced OKT8- and WGA-binding cells concurrently, whereas treatment with OKT4 and complement did not reduce percentages of either type of cell. Similarly, specific depletion of OKT8-binding cells abolished the mitogenic response to WGA but not that to PHA. Cell populations enriched for WGA-binding cells prepared by flow cytometry and cell sorting demonstrated parallel enrichment for OKT8-binding and depletion of OKT4-binding cells. Therefore, these data demonstrate specific inhibition of OKT4 and OKT8 binding by the lectins, RCA-I and WGA, respectively. Inhibition was mediated by lectin binding to lymphoid cell surfaces, perhaps directly to the T4 or T8 antigens. The observations indicate that lectins may prove useful for investigating structural features of some immunologic cell surface markers. Furthermore, they provide the possibility that certain in vitro effects of lectins on immune function may result from their interactions with molecules such as the T4 and T8 antigens.

Animals↗
PubMed1983

Phytohemagglutinin derived from red kidney bean (Phaseolus vulgaris): a cause for intestinal malabsorption associated with bacterial overgrowth in the rat.

Plant lectins or carbohydrate binding proteins interact with membrane receptors on cellular surfaces but their antinutritional effects are poorly defined. Studies were conducted to determine the effects of phytohemagglutinin, a lectin derived from raw red kidney bean (Phaseolus vulgaris), on small intestinal absorptive function and morphology, and on the intestinal microflora. Phytohemagglutinin was isolated in purified form by thyroglobulin-sepharose 4B affinity chromatography. Red kidney bean and phytohemagglutinin (6% and 0.5%, respectively, of dietary protein) were fed in a purified casein diet to weanling rats for up to 21 days. Weight loss, associated with malabsorption of lipid, nitrogen, and vitamin B12, developed in comparison with animals pair-fed isonitrogenous casein diets. Antinutritional effects of red kidney bean were reversible on reinstitution of a purified casein diet. An increase in bacterial colonization of the jejunum and ileum occurred in red kidney bean- and phytohemagglutin-fed animals. When antibiotics were included in the diet, malabsorption of [3H]triolein and 57Co-vitamin B12 in red kidney bean-fed animals was partially reversed and, in germ-free animals, purified phytohemagglutinin had no demonstrable antinutritional effect. Mucosal disaccharidase activity was reduced in red kidney bean- and phytohemagglutinin-fed animals, but intestinal mucosal morphology was unchanged. Dietary administration of phytohemagglutinin, alone or as a component of red kidney bean, caused intestinal dysfunction, which was associated with, and dependent upon, small intestinal bacterial overgrowth. Adherence of enteric bacteria to the mucosal surface was enhanced by phytohemagglutinin which may have facilitated small intestinal bacterial overgrowth.

Animals↗
PubMed1983

Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase.

We have studied the effects of tamoxifen on the cell cycle kinetics of the endocrine-responsive MCF-7 human breast cancer cells. Tamoxifen inhibits proliferation of MCF-7 cells. The tritiated thymidine labeling index is markedly reduced by tamoxifen, indicating a reduction in the fraction of cells in S phase. Flow cytometry of mithramycin-stained cells reveals that cells accumulate in G1 phase, with a concomitant depletion of S- and G2-M-phase cells with tamoxifen. Mapping of G1-phase cells by morphology of prematurely condensed chromosomes demonstrated that tamoxifen-treated cells accumulate in early G1. These studies indicate that tamoxifen inhibits proliferation of MCF-7 human breast cancer cells by invoking a transition delay early in the G1 phase of the cell cycle.

Breast Neoplasms↗
PubMed1982

Chronic lymphocytic leukemia: demonstration of cell surface structural heterogeneity by lectin affinity chromatography of cell extracts.

I have used lectin affinity chromatography of radiolabelled components in cell extracts to examine molecular heterogeneity of membrane glycoproteins from 10 cases of chronic lymphocytic leukemia (CLL). Different complements of radiolabelled surface glycoproteins were found in extracts from cells with different lectin binding characteristics. Additional confirmation of heterogeneity was obtained by analyses of hexose and sialic acid contents of the extracts and various lectin-adherent fractions. The fact that CLL cells from different patients may carry different cell surface oligosaccharides provides the possibility that clinical variability in this disorder may relate in part to this molecular heterogeneity. The data further indicate that different lectins may bind to different saccharide structures at CLL cell surfaces. CLL cells represent excellent source material for isolation and purification of specific lectin receptor molecules.

Cell Extracts↗
PubMed1982

Cell surface alpha 1-protease inhibitor on human peripheral mononuclear cells in culture.

We have studied expression of alpha 1-protease inhibitor (alpha 1-PI) by human mononuclear cells. alpha 1-PI was detected on 50% of freshly isolated peripheral mononuclear cells. Unless a proliferative stimulus was provided, alpha 1-PI subsequently disappeared from the cell surfaces. Plant mitogens, periodate, neuraminidase-galactose oxidase, or allogeneic cells all were effective stimuli of alpha 1-PI expression. Concanavalin A stimulated de novo synthesis of alpha 1-PI in cell cultures containing both lymphocytes and mononuclear phagocytes, and alpha 1-PI simultaneously appeared on surfaces of activated lymphocytes. Inhibition of protein synthesis by cycloheximide or monocyte depletion abolished de novo alpha 1-PI synthesis, but only monocyte depletion inhibited alpha 1-PI expression. Lymphocytes, but not monocytes, displayed saturable binding of radioiodinated alpha 1-PI. The data are consistent with the interpretation that human mononuclear phagocytes synthesize and secrete alpha 1-PI. When protein synthesis is inhibited, mitogenic stimuli may provoke release of previously synthesized alpha 1-PI from mononuclear phagocytes. Secreted alpha 1-PI then may bind to specific lymphocyte cell surface receptors. This pattern of alpha 1-PI synthesis, secretion, binding, and expression on lymphoid cell surfaces appears to be a common characteristic of many immunologic reactions in vitro.

B-Lymphocytes↗