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Biomedical subjects

R Yoshimoto

Publications and source records attributed to R Yoshimoto.

At least 37 records · Page 2Linked to original sources
PubMed1999

Selectivity of dihydropyridines for cardiac L-type and sympathetic N-type Ca2+ channels.

The blocking effects of cilnidipine and other dihydropyridines on L-type cardiac Ca2+ channels (I(Ca,L)) and N-type sympathetic Ca2+ channel currents (I(Ca,N)) were studied using a whole-cell patch-clamp technique. At -80 mV, cilnidipine had little inhibitory effect below concentrations of 1 microM on I(Ca,L) (IC50 value; 17 microM). However, 1 microM cilnidipine strongly shifted the steady-state inactivation curve of I(Ca,L) toward negative potentials without changing the current-voltage relationship. Each action of cilnidipine was characterized by a high affinity for the inactivated channel in preference to the resting channel. The IC50 values of dihydropyridines for I(Ca,L) were in the range between 0.01 and 10 microM, and those for I(Ca,N) were between 3 and 30 microM. Cilnidipine had the strongest affinity for I(Ca,N) among the dihydropyridines tested. These results suggest that cilnidipine did not cause hypotension-evoked tachycardia deficiency by depression of cardiac L-type channels but by sympathetic N-type channels blockade.

Animals↗
PubMed1999

Effects of AH-1058, a new antiarrhythmic drug, on experimental arrhythmias and cardiac membrane currents.

AH-1058 is a newly synthesized antiarrhythmic agent. We investigated the antiarrhythmic and electrophysiological effects of AH-1058 in experimental arrhythmia models and isolated cardiomyocytes. In the ouabain-induced arrhythmia model of the guinea pig, pretreatment with AH-1058 (0.1-0.3 mg/kg, i.v.) delayed the appearance of premature ventricular complex (PVC) and ventricular fibrillation (VF) induced by intravenous infusion of ouabain. However, disopyramide (10 mg/kg, i.v.) delayed only that of PVC, and verapamil (1 mg/kg, i.v.) failed to affect the ouabain-induced ventricular arrhythmias. In the reperfusion-induced arrhythmia model of the rat, in which 5-min coronary occlusion and 10-min reperfusion were produced, AH-1058 (0.1-0.3 mg/kg, i.v.) inhibited the incidence of both ventricular tachycardia (VT) and VF, whereas disopyramide (5 mg/kg, i.v.) inhibited only reperfusion-induced VF. On the other hand, a higher dose of AH-1058 (1 mg/kg, i.v.) did not affect the aconitine-induced arrhythmias in rats, which were inhibited by disopyramide (5 mg/kg, i.v.). We also confirmed oral activity of AH-1058 in the reperfusion-induced arrhythmia model of the rat. AH-1058, at doses of 2-4 mg/kg, dose-dependently inhibited VT and VF. Electrophysiological experiments with patch-clamp techniques revealed that AH-1058 potently suppressed the L-type Ca2+ currents in isolated cardiomyocytes of the guinea pig. These results suggest that AH-1058 is a potent antiarrhythmic drug having a Ca2+ channel-blocking action. The antiarrhythmic profile of AH-1058 is different from that of disopyramide and verapamil.

Aconitine↗
PubMed1999

AJvW-2, an anti-vWF monoclonal antibody, inhibits enhanced platelet aggregation induced by high shear stress in platelet-rich plasma from patients with acute coronary syndromes.

The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesis that occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm2) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 microgram/mL AJvW-2. Under low-shear conditions (12 dyne/cm2), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries.

Acute Disease↗
PubMed1999

[Actin depolymerizing action by marine toxin, pectenotoxin-2].

Pectenotoxin-2 (PCTX-2), which is one of Diarrhetic Shellfish Poisoning (DSP), is a family of cyclic polyether macrolide toxin isolated from scallop Patinopecten yessoensis. Although PCTX-2 has a potent cytotoxic activities against several cancer cell lines, the biochemical activity of PCTX-2 has not been determined yet. To clarify the biochemical activity of PCTX-2 is the aime in this study. PCTX-2 inhibited the contractions elicited by 72.7 mM KCl or 1 microM phenyrephrine in a concentration dependent manner in the isolated rat aorta. In A10 cells, actin stressfiber in center but not in periphery of the cell was disrupted by PCTX-2 without any visible shape change. By monitoring fluorescent intensity of pyrenyl-actin, PCTX-2 was found to inhibit the velocity and the degree of actin polymerization in a concentration dependent manner. In addition, PCTX-2 decreased viscosity of F-actin measured with falling ball viscometry. Stoichiometric analysis indicated that PCTX-2 forms 1:4 complex with G-actin. These results suggest that PCTX-2 is a potent natural actin depolymerizing compound with unique mode of action.

Actins↗
PubMed1999

Pharmacology of N-type Ca2+ channels distributed in cardiovascular system (Review).

Irregular functions in Ca2+ channels are intimately involved in many aspects of cardiovascular diseases. We can obtain a wide variety of L-type Ca2+ channel antagonists to treat hypertension and angina pectoris. Dihydropyridines (DHPs) have, first of all, been extensively developed due to their high selectivity for L-type Ca2+ channel and safety in pharmacological aspects. In contrast, many lines of evidence suggest that clinical efficacy of those DHPs are limited and undesirable effects are sometimes observed because of the specific distribution of L-type Ca2+ channels. As well as the L-type, peripherally distributed N-type Ca2+ channel plays a key role in cardiovascular regulation through autonomic nervous system. Recently, we developed a unique DHP derivative, cilnidipine (FRC8653) which has a dual antagonistic action on both L-type and N-type Ca2+ channels. Our recent studies with this DHP have made it clear that the N-type Ca2+ channel is also a new therapeutic target in cardiovascular diseases. We review the recent advances in pharmacology of the N-type Ca2+ channel and therapeutic implications of their antagonists.

Amino Acid Sequence↗
PubMed1998

Effects of adrenomedullin and calcitonin gene-related peptide on contractions of the rat aorta and porcine coronary artery.

1. Effects of adrenomedullin and alpha-calcitonin gene-related peptide (CGRP) on the contractions and cytosolic Ca2+ concentrations ([Ca2+]i) of the rat aorta and porcine coronary artery were investigated. Characteristics of the receptors mediating the effects of adrenomedullin and alpha-CGRP were also investigated. 2. Adrenomedullin and alpha-CGRP caused a concentration-dependent relaxation in the rat aorta contracted with noradrenaline. The IC50 values for adrenomedullin and alpha-CGRP were 2.4 nM and 4.0 nM, respectively. The relaxant effects of these peptides were abolished by removal of the endothelium and significantly attenuated by an inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (L-NMMA, 100 microM), but not by a cyclo-oxygenase inhibitor, indomethacin (10 microM). 3. Adrenomedullin and alpha-CGRP increased the endothelial [Ca2+]i in the rat aorta with endothelium, whereas they did not change [Ca2+]i in the smooth muscle. 4. An antagonist of the CGRP1 receptor, CGRP (8-37), antagonized the relaxant effects of alpha-CGRP and the beta-isoform of CGRP (beta-CGRP) but not those of adrenomedullin in the rat aorta. 5. In the porcine coronary artery contracted with U46619, adrenomedullin and alpha-CGRP caused a concentration-dependent relaxation with an IC50 of 27.6 and 4.1 nM, respectively. Removal of the endothelium altered neither the IC50 values nor the maximal relaxations induced by adrenomedullin or alpha-CGRP. When the artery was contracted with high K+ solution (72.7 mM), these peptides caused a small relaxation. 6. Adrenomedullin and alpha-CGRP increased cyclic AMP content and decreased the smooth muscle [Ca2+]i in the porcine coronary artery. 7. CGRP (8-37) significantly antagonized the relaxant effects of adrenomedullin and alpha-CGRP in the porcine coronary artery. However, it had little effect on the relaxations induced by the beta-isoform of CGRP (beta-CGRP). 8. These results suggest that in the rat aorta, adrenomedullin and alpha-CGRP increase the endothelial [Ca2+]i, activate nitric oxide synthase and release nitric oxide, without a direct inhibitory action on smooth muscle. In the porcine coronary artery, in contrast, adrenomedullin and alpha-CGRP directly act on smooth muscle, increase cyclic AMP content, decrease the smooth muscle [Ca2+]i and inhibit contraction. The rat aortic endothelium seems to express the CGRP receptor which is sensitive to alpha-CGRP, beta-CGRP and CGRP (8-37) and the adrenomedullin specific receptor. The porcine coronary smooth muscle, in contrast, seems to express two types of CGRP receptor; one of which is sensitive to alpha-CGRP, CGRP (8-37) and adrenomedullin and the other is sensitive only to beta-CGRP.

Adrenomedullin↗
PubMed1998

Effects of a novel antihypertensive drug, cilnidipine, on catecholamine secretion from differentiated PC12 cells.

Effects of a novel dihydropyridine type of antihypertensive drug, cilnidipine, on the regulation of the catecholamine secretion closely linked to the intracellular Ca2+ were examined using nerve growth factor (NGF)-differentiated rat pheochromocytoma PC12 cells. By measuring catecholamine secretion with high-performance liquid chromatography coupled with an electrochemical detector, we showed that high K+ stimulation evoked dopamine release from PC12 cells both before and after NGF treatments. Cilnidipine depressed dopamine release both from NGF-treated and untreated PC12 cells in a concentration-dependent manner. In contrast, inhibition by nifedipine was markedly decreased in the differentiated PC12 cells. With intracellular Ca2+ concentration ([Ca2+]i) measurements using fura 2, the elevation of high K+-evoked [Ca2+]i was separated into nifedipine-sensitive and -resistant components. The nifedipine-resistant [Ca2+]i increase was also blocked by cilnidipine, as well as omega-conotoxin-GVIA. By the use of the conventional whole-cell patch-clamp technique, the compositions of the high-voltage-activated Ca2+ channel currents in the NGF-treated PC12 cells were divided into types: L-type, N-type, and residual current components. It was also estimated that cilnidipine at 1 and 3 micromol/L strongly blocked the N-type current without affecting the residual current. These results suggest that cilnidipine inhibits catecholamine secretion from differentiated PC12 cells by blocking Ca2+ influx through the N-type Ca2+ channel, in addition to its well-known action on the L-type Ca2+ channel.

Animals↗
PubMed1998

Antagonism of vWF inhibits both injury induced arterial and venous thrombosis in the hamster.

von Willebrand factor (vWF) is instrumental in arterial but has also been implicated in venous thrombogenesis. To address its role in venous thrombosis, experimental thrombosis was induced in the carotid artery and the femoral vein of hamsters, following which thrombus prevention by two different antagonists of vWF was studied. The first antagonist was the anti-human vWF monoclonal antibody AJvW-2, which inhibits the botrocetin and ristocetin induced aggregation of human blood platelets. AJvW-2 reacts with an epitope present in the A1 domain of vWF in very different species (human, pig, rabbit, dog, Guinea pig and rat). This epitope was found to be conformational and overlapping with vWF binding sites for aurin tricarboxylic acid (ATA), but not for botrocetin and heparin. AJvW-2 has affinities for vWF in the absence (Kd = 0.5 +/- 0.03 nmol/l in solution) and in the presence of shear stress (Kd = 3.3 +/- 0.6 nmol/l during perfusion at 1,300 s over subendothelial matrix associated vWF) sufficiently elevated to neutralize vWF. During perfusion of subendothelial matrix with anticoagulated human blood, the surface covered by adhering platelets was reduced by AJvW-2, with IC50s equal to 6.6 +/- 0.34 microg/ml at 1,300 s(-1) and to 1 +/- 0.01 microg/ml at 2,700 s(-1). As a second antagonist, molecular size gel filtered ATA was selected. Fractionated ATA inhibited platelet adhesion to matrix with IC50s equal to 0.27 +/- 0.09 mmol/l at 1,300 s(-1) and 0.16 +/- 0.008 mmol/l at 2,700 s(-1). When administered to hamsters, AJvW-2 prevented thrombosis in the injured carotid artery dose-dependently (ED50 = 0.15 +/- 0.01 mg/kg). Thrombosis in the similarly injured femoral vein was however also inhibited (ED50 = 0.37 +/- 0.06 mg/kg). Likewise, fractionated ATA completely inhibited carotid artery thrombosis (ED50 = 0.42 +/- 0.13 mg/kg), but also interfered with femoral vein thrombosis (apparent ED50 between 2 and 3 mg/kg). We conclude that antagonizing the vWF A1 domain by AJvW-2 and to a lesser extent also by fractionated ATA, inhibits thrombosis not only in the arterial but also in the venous circulation. Since venous thrombi were prevented at only 3-5-fold higher doses of antagonist, vWF participates in injury induced venous thrombosis.

Animals↗
PubMed1997

Blockade of N-type Ca2+ current by cilnidipine (FRC-8653) in acutely dissociated rat sympathetic neurones.

1 The inhibitory effects of cilnidipine (FRC-8653) and various organic Ca2+ channel blockers on high voltage-activated Ba2+ currents (HVA IBa) in rat sympathetic neurones were examined by means of the conventional whole-cell patch-clamp recording mode under voltage-clamped conditions. 2 HVA IBa was classified into three different current components with subtype selective peptide Ca2+ channel blockers. No omega-Agatoxin IVA-sensitive (P-type) or omega-conotoxin MVIIC-sensitive (Q-type) current components were observed. Most (> 85%) IBa was found to consist of omega-conotoxin GVIA-sensitive N-type components. 3 The application of cilnidipine inhibited HVA 1Ba in a concentration-dependent manner. The Kd value for cilnidipine was 0.8 microM. Cilnidipine did not shift the current-voltage (I-V) relationship for HVA IBa, as regards the threshold potential and peak potential where the amplitude reached a maximum. 4 High concentration of three hypotensive Ca2+ channel blockers, nifedipine, diltiazem and verapamil, all inhibited HVA IBa in a concentration-dependent manner. The Kd values for nifedipine, diltiazem and verapamil were 131, 151 and 47 microM, respectively. A piperazine-type Ca2+ channel blocker, flunarizine, showed a relatively potent blocking action on IBa. The Kd value was about 3 microM. 5 These results thus show that cilnidipine potently inhibits the sympathetic Ca2+ channels which predominantly consist of an omega-Cg-GVIA-sensitive component. This blockade of the N-type Ca2+ channel, as well as the L-type Ca2+ channel by cilnidipine suggests that it could be used therapeutically for treatment of hypersensitive sympathetic disorders associated with hypertension.

Animals↗
PubMed1997

Anti-thrombotic effects and bleeding risk of AJvW-2, a monoclonal antibody against human von Willebrand factor.

1. A murine anti-human vWF monoclonal antibody, AJvW-2, was developed that inhibited the interaction between platelet glycoprotein Ib (GPIb) and von Willebrand factor (vWF) during the ristocetin- (IC50 = 0.7 +/- 0.1 microgram ml-1) and botrocetin- (IC50 = 1.8 +/- 0.3 microgram ml-1) induced aggregation of human platelets. 2. AJvW-2 inhibited the high shear stress (10.8 N m-2) induced aggregation of human platelets dose-dependently with an IC50 = 2.4 +/- 0.3 micrograms ml-1, but had no effect on low shear stress induced platelet aggregation (1.2 N m-2) up to 100 micrograms ml-1. 3. AJvW-2 also inhibited the high shear stress (5.0 N m-2) induced adhesion of human platelets to collagen I with the same efficacy (IC50 = 2.4 +/- 0.3 micrograms ml-1), but no effect at low shear conditions (1.5 N m-2). 4. AJvW-2 inhibited the botrocetin-induced aggregation of platelets from guinea-pig, rat, rabbit, dog and pig at the same concentration range as human platelets; it likewise also inhibited the high shear stress induced aggregation and adhesion to collagen I of guinea-pig platelets. 5. AJvW-2 prevented arterial thrombus formation in guinea-pigs at a dose of 100 micrograms kg-1 without prolonging the template bleeding time, whereas the GPIIb/IIIa antagonists lamifiban mediated inhibition of thrombosis at 1000 micrograms kg-1 was accompanied by a significant prolongation of the bleeding time. 6. These results suggest that AJvW-2 is a potent inhibitor of the GPIb-vWF interaction and a potential novel antithrombotic agent with lower bleeding risk than GPIIb/IIIa antagonists.

Animals↗
PubMed1997

Cilnidipine attenuates renal nerve stimulation-induced renal vasoconstriction and antinatriuresis in anesthetized dogs.

We examined the effects of cilnidipine, which is an L- and N-type Ca2+ channel blocker, on adrenergically regulated renal functions in anesthetized dogs. Renal nerve stimulation (RNS) at high frequency (3-7 Hz) decreased renal blood flow (RBF) without changes in systemic blood pressure. The RBF response was inhibited by intrarenal arterial (i.r.a.) infusion of cilnidipine at 0.1-0.3 microgram/kg/min. Low-frequency RNS (0.5-1 Hz) reduced absolute and fractional urinary sodium excretion. These responses were attenuated during i.r.a. infusion of cilnidipine at 0.3 microgram/kg/min. An increase in norepinephrine secretion rate induced by low-frequency RNS was also attenuated during cilnidipine infusion. These results suggest that cilnidipine can suppress norepinephrine release from the renal nerve endings and thereby interfere with the neural control of renal functions.

Anesthesia↗
PubMed1995

[Antihypertensive effects of repeated oral administration of cilnidipine, a novel calcium antagonist, in 2K1C renal hypertensive dogs].

Antihypertensive effects of repeated oral administration of cilnidipine in 2K1C renal hypertensive dogs were compared with those of nicardipine. On the first day, oral administration of cilnidipine (3 mg/kg) or nicardipine (3 mg/kg) markedly lowered both systolic and diastolic blood pressure 1 hr after administration. The hypotensive effects of cilnidipine were longer compared with those of nicardipine. Both drugs elevated the heart rate and plasma renin activity. On the 8th and 15th days, similar responses were obtained by repeated administrations of cilnidipine and nicardipine. After withdrawal of these drugs, no rebound phenomena in blood pressure were observed. The changes in mean blood pressure were correlated with plasma cilnidipine or nicardipine concentrations that were obtained at each time of blood pressure measurement (r = -0.598; P < 0.001 and r = -0.594; P < 0.001, respectively). These results suggest that stable and long-acting antihypertensive effects of cilnidipine for 15 consecutive days in renal hypertensive dogs are related to the change in plasma drug concentrations.

Administration, Oral↗
PubMed1992

Effects of a new dihydropyridine derivative, FRC-8653, on blood pressure in conscious spontaneously hypertensive rats.

Antihypertensive effects of FRC-8653, a new 1,4-dihydropyridine derivative, and its combined effects with an angiotensin converting enzyme (ACE) inhibitor, a diuretic, and a beta-adrenergic blocking agent were examined in conscious spontaneously hypertensive rats (SHR). When administered intravenously to SHR (10, 30 micrograms/kg), FRC-8653 lowered blood pressure more slowly and sustained it longer than nifedipine and nicardipine. Consecutive once-daily administrations of FRC-8653 to SHR (3 mg/kg, p.o.) produced a stable reduction of blood pressure throughout the experimental period of 29 d. When blood pressure was continuously measured for 24 h in conscious unrestricted SHR, orally administered FRC-8653 produced a long-lasting reduction in blood pressure. When concomitantly used with atenolol (30 mg/kg, p.o.), the antihypertensive effect of FRC-8653 was augmented in both potency and duration. However, simultaneous administration of captopril (30 mg/kg, p.o.) or hydrochlorothiazide (2.5 mg/kg, p.o.) did not modify the antihypertensive effect of FRC-8653.

Animals↗
PubMed1992

In vitro and ex vivo Ca-antagonistic effect of 2-methoxyethyl(E)-3-phenyl-2-propen-1-yl(+/-)-1,4-dihydro-2,6-dimethyl- 4-(3- nitrophenyl)pyridine-3,5-dicarboxylate (FRC-8653), a new dihydropyridine derivative.

The characteristics of calcium antagonism and vascular effect of 2-methoxyethyl(E)-3-phenyl-2-propen-1-yl(+/-)-1,4-dihydro-2,6-dime thyl-4-(3- nitrophenyl)pyridine-3,5-dicarboxylate (FRC-8653) were investigated. FRC-8653 inhibited an increase in intracellular free calcium concentration during membrane depolarization in PC12 cells. FRC-8653 also inhibited the specific binding of 3H-nitrendipine to cardiac membranes, in a similar manner to nifedipine and nicardipine. FRC-8653 inhibited KCl- and CaCl-induced contractions in isolated rabbit aorta, but failed to affect norepinephrine-induced contraction. The vasorelaxing effect of FRC-8653 in rabbit aorta developed more slowly than those of nifedipine and nicardipine. In ex vivo experiment, the inhibitory effect of orally administered FRC-8653 against KCl-contraction in rat aorta lasted longer than that of nifedipine. These findings suggest that FRC-8653 dilates blood vessels by blocking calcium influx via dihydropyridine-sensitive, voltage-dependent calcium channels and that the vascular effects are slow in development and long in duration.

Animals↗
PubMed1991

Prolonged inhibition of vascular contraction and calcium influx by the novel 1,4-dihydropyridine calcium antagonist cinaldipine (FRC-8653).

We examined the effects of FRC-8653, a novel dihydropyridine calcium antagonist, on the contraction of an arterial preparation and the calcium influx into vascular smooth muscle cells to clarify the long-lasting hypotensive activity of this drug. Inhibition by FRC-8653 persisted for more than 7 hr after its removal, whereas nifedipine and nicardipine exhibited shorter durations of suppressive activity. These results suggest that prolonged inhibition of calcium influx through L-channels contributes to the long-lasting vasodilative and antihypertensive activity of FRC-8653.

Animals↗
PubMed1987

Plant lectin, ATF1011, on the tumor cell surface augments tumor-specific immunity through activation of T cells specific for the lectin.

The possibility that a plant lectin as a carrier protein would specifically activate T cells, resulting in the augmentation of antitumor immunity was investigated. ATF1011, a nonmitogenic lectin for T cells purified from Aloe arborescens Mill, bound equally to normal and tumor cells. ATF1011 binding on the MM102 tumor cell surfaces augmented anti-trinitrophenyl (TNP) antibody production of murine splenocytes when the mice were primarily immunized with TNP-conjugated MM102 tumor cells. The alloreactive cytotoxic T cell response was also augmented by allostimulator cells binding ATF1011 on the cell surfaces. These augmented responses may be assumed to be mediated by the activation of helper T cells recognizing ATF1011 as a carrier protein. Killer T cells were induced against ATF1011 antigen in the H-2 restricted manner using syngeneic stimulator cells bearing ATF1011 on the cell surfaces. When this lectin was administered intralesionally into the tumors, induction of cytotoxic effector cells was demonstrated. These results suggest that intralesionally administered ATF1011 binds to the tumor cell membrane and activates T cells specific for this carrier lectin in situ, which results in the augmented induction of systemic antitumor immunity.

Animals↗
PubMed1986

A T cell leukemia line produces factor(s) that render rat neutrophils cytotoxic.

Proteose-peptone-induced intraperitoneal neutrophils from rats were activated in terms of tumor cytotoxicity by pretreatment with culture supernatants from a human T cell leukemia line, Jurkat (culture sup). Culture sup-treated neutrophils showed cytotoxicity against various tumor cell lines. The cytotoxicity of culture sup-treated neutrophils was dependent on the number of neutrophils and the concentration of culture sup. Cytostasis by activated neutrophils was observed very early in the assay incubation period (within 6 hr), but cytolysis first occurred at 24 hr after the start of incubation. Factor(s) in culture sup responsible for the activation of cytotoxic neutrophils were stable to temperature and pH treatments, and their molecular weight was higher than 10,000. The responsible factor(s) for activation of cytotoxic neutrophils were different from interleukin-2, serum-derived factor, and bacterial lipopolysaccharide.

Animals↗