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L Jakoi

Publications and source records attributed to L Jakoi.

30 records · Page 2Linked to original sources
PubMed1987

Role of a guanine nucleotide regulatory protein in the activation of phospholipase C by different chemoattractants.

It is well established that formyl peptide chemoattractants can activate a phospholipase C in leukocytes via a pertussis toxin (PT)-sensitive guanine nucleotide regulatory (G) protein. Whether this pathway is similarly used by chemoattractant receptors as a class has been unclear. We now report that lipid and peptide chemoattractants in direct comparative studies induced similar amounts of initial (less than or equal to 15 sec) inositol trisphosphate (IP3) release in human polymorphonuclear leukocytes, but the response to lipid chemoattractants was more transient. Production of IP3 by all chemotactic factors was inhibited by treatment of the cells with PT, indicating that chemotactic factor receptors as a class are coupled to phospholipase C via a G protein that is a substrate for ADP ribosylation by PT. The peptide and lipid factors had comparable chemotactic activity, which was also inhibitable by PT. However, transient activation of phospholipase C is apparently an insufficient signal for full cellular activation, since the lipid chemotactic factor leukotriene B4 and platelet-activating factor were poor stimuli for O2- production and lysosomal enzyme secretion compared with N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe). Nonetheless, treatment with PT inhibited O2- production and enzyme secretion in response to all chemoattractants, but as previously noted, did not affect Ca2+ ionophores, lectins, or phorbol myristate acetate. Formyl peptide and lipid chemotactic factors induced similar levels of Ca2+ mobilization when monitored by Quin 2 or chlortetracycline (CTC) fluorescence. Although these responses to fMet-Leu-Phe were blocked by PT, the Quin 2 and initial CTC response to the lipid factors were only partially susceptible. Thus, the lipid factors apparently utilize an additional PT-resistant mechanism for redistributing intracellular Ca2+. This latter process requires extracellular Ca2+ and may be independent of the PT-sensitive G protein.

Calcium↗
PubMed1986

A guanine nucleotide regulatory protein controls polyphosphoinositide metabolism, Ca2+ mobilization, and cellular responses to chemoattractants in human monocytes.

Previous studies demonstrated that oligopeptide chemoattractant receptors on PMN and macrophages exist in high and low affinity states which are interconvertible by guanosine di- and triphosphates. These observations suggest that guanine nucleotide regulatory (N) proteins play a role in phagocyte activation by chemotactic factors. The data presented here indicate that chemotactic factor receptors on monocytes utilize an N protein to activate phospholipase C and subsequent biologic responses by the cells. This conclusion is based on the findings that inactivation of an N protein of 41,000 m.w. by Bordetella pertussis toxin (PT) treatment abolishes monocyte responsiveness to chemoattractants but not to lectins, PMA, or the Ca2+ ionophore A23187. Treatment with PT inhibited IP3 production, Ca2+ mobilization, and cellular activation as assessed by chemotaxis and changes in forward light scattering in response to the chemoattractants by at least 80%. Therefore, a PT-sensitive N protein plays an important role in the activation of monocytes by chemoattractants.

Adenosine Diphosphate Ribose↗
PubMed1986

Chemoattractant-mediated stimulation of the respiratory burst in human polymorphonuclear leukocytes may require appearance of protein kinase activity in the cells' particulate fraction.

Low doses of aliphatic alcohols produce divergent effects on the function of chemoattractant receptors on human polymorphonuclear leukocytes (PMNs) since they enhance chemotaxis but inhibit stimulation of superoxide production by chemoattractants. As such, alcohols can provide useful pharmacologic tools to probe the mechanisms of stimulus-response coupling in leukocytes. A role for protein kinase C has been implicated in the activation of the respiratory burst in PMNs. Although the vast majority of this enzyme activity is located in the cytosolic fraction of unactivated PMNs, protein kinase C activity appears in the particulate fraction of the cells when they are stimulated to produce superoxide by either chemoattractants or by phorbol myristate acetate (PMA). Doses of the alcohols that selectively inhibited stimulation of superoxide production by chemoattractants also inhibited the appearance of protein kinase C activity as well as an undefined protein kinase activity in the particulate fraction of the cells. In contrast, the alcohols did not affect either the ability of PMA to stimulate the production of superoxide in PMNs nor the appearance of protein kinase activity in the cells' particulate fraction. PMA is known to bind and activate protein kinase C directly, thus bypassing receptor-mediated events. These data suggest that alcohols inhibit the stimulation of the respiratory burst by chemoattractants in PMNs by blocking the ability of receptor occupancy to induce the appearance of protein kinase activity in particulate fractions. These results moreover suggest that the appearance of protein kinase activity in the particulate fraction may be required for activation of the respiratory burst in PMNs.

Alcohols↗
PubMed1983

Polymorphonuclear leukocyte function in psoriasis: chemotaxis, chemokinesis, beta-adrenergic receptors, and proteolytic enzymes of polymorphonuclear leukocytes in the peripheral blood from psoriatic patients.

Psoriatic patients, particularly those with psoriatic arthritis, have neutrophilic and eosinophilic leukocytosis. Isolated polymorphonuclear leukocytes (PMNLs) from psoriatic patients have normal concentrations of proteolytic enzymes and they have beta-adrenergic receptors of normal density and affinity. PMNLs from psoriatic patients responded normally to the synthetic chemotactic peptide, f-Met-Leu-Phe (formyl-methionine-leucine-phenylalanine). The chemotactic activities of sera from psoriatic patients were similar to those of normal sera. Sera from psoriatic patients enhanced chemokinesis of PMNLs more than normal control sera at a final concentration of 1%; no difference in chemokinetic response between psoriatic and normal sera was found at serum concentrations greater than 2.5%. This study suggests that the peripheral PMNLs from psoriatic patients are normal, but the sera of psoriatic patients has more chemokinetic activity for PMNLs than does normal serum.

Chemotaxis, Leukocyte↗
PubMed1981

Effect of apolipoproteins on the induction of hepatic steatosis in rats.

The incorporation of apolipoprotein E isolated from human very low density lipoproteins on a triglyceride emulsion produced a substantial increment in hepatic triglyceride after 1 h of in vitro perfusion through the isolated liver of a fasted rat. Both gross and microscopic morphology confirmed a substantial steatosis. Perfusions with triglyceride emulsions which contained no apoipoproteins resulted in a modest increment in hepatic triglyceride although considerably less than emulsions with the E protein, and no morphologic features of steatosis. The steatosis induced in the in vitro perfused fasted livers by the emulsions with E protein could be prevented when CIII-1 apoprotein was also incorporated on the emulsion. A fed rat liver perfused with the E-enriched emulsion accumulated significantly less triglyceride than the fasted preparation. These data suggest that the apoprotein patterns of the plasma triglyceride-rich lipoproteins are of considerable importance for the partition of triglyceride between liver and plasma.

Animals↗
PubMed1980

Selective biliary secretion of basal and glucagon-inhibited neutral sterol after triparanol administration.

Biliary cholesterol secretion was studied in dogs with chronic bile fistulas, using glucagon, an inhibitor of biliary cholesterol secretion, and triparanol, an inhibitor of cholesterol synthesis. Glucagon inhibited neutral sterol secretion before and after triparanol administration. Triparanol caused a significant accumulation in bile of the cholesterol precursor desmosterol which comprised a significant portion of the neutral sterol in bile but not in blood. Glucagon inhibited both biliary desmosterol and cholesterol secretions to a similar degree. These findings suggest that biliary cholesterol is derived from newly synthesized hepatic sterol as well as from equilibrated sources. Furthermore, glucagon suppressed biliary secretion of both equilibrated as well as newly synthesized neutral sterol, suggesting that glucagon inhibits the movement of neutral sterol to or through the canalicular membrane.

Animals↗
PubMed1978

The sources of rat biliary cholesterol and bile acid.

The precursor sources of bile acid and bile neutral sterol were evaluated in the rat using Triparanol to inhibit the terminal reduction in the synthesis of cholesterol. During the initial period of Triparanol administration, the accumulation of hepatic desmosterol acts to segregate relatively newly synthetic hepatic sterol from the bulk of the equilibrated sterol mass. Biliary excretion of newly synthetic sterol can then be determined in acute studies, assuming no great differences between desmosterol and cholesterol as precursors of biliary neutral sterol or bile acid. It has been determined in this model that newly synthetic sterol comprises a mean of about 28% of the total biliary neutral sterol output. This fraction fell when hepatic cholesterogenesis was suppressed by prior cholesterol feeding. By using this approach in conjunction with the administration of labeled mevalonate to a renal pedicle-ligated rat, it was possible to calculate the amount of bile acid produced from either newly synthesized sterol or the equilibrated sterol pool. It has been estimated that the bulk of bile acid synthesis arises from this equilibrated source when these determinations were made within two hours of creating the fistula. With more prolonged fistula times, more of the bile acid originated from the newly synthesized sterol.

Animals↗
PubMed1977

Alterations of rat hepatic cholesterogenesis by heterologous lipoproteins.

Heterologous human lipoproteins were infused into rats in order to change acutely the lipoprotein pattern to a predominant kind and the effect on hepatic cholesterogenesis was subsequently observed. A 4-h intravenous infusion of human low density and very low density lipoproteins into rats produced a significant decrease in the incorporation of acetate into cholesterol in both liver slices and homogenates. An infusion of similar concentrations of human high density lipoprotein produced a significant increase in hepatic cholesterol synthesis. These infusions did not change mevalonate conversion to cholesterol in either the homogenates or slices. Concomitant with the changes in hepatic cholesterol synthesis were changes of similar magnitudes in the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. These alterations in hepatic cholesterol synthesis were associated with significant changes in microsomal cholesterol content. There was a significant increase in hepatic cholesterol synthesis with the infusion of apoproteins of high density lipoprotein. The apoproteins of very low density lipoprotein had no effect on hepatic cholesterogenesis. These studies indicate that circulating lipoproteins modify hepatic cholesterol synthesis and that the apoproteins of these lipoproteins may themselves be important for this action.

Acetates↗