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E Kubota

Publications and source records attributed to E Kubota.

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

Zonal heterogeneity in action of angiotensin-converting enzyme inhibitor on renal microcirculation: role of intrarenal bradykinin.

The present study examined the role of intrarenal bradykinin in angiotensin-converting enzyme inhibitor (ACEI)-induced dilation of renal afferent (AFF) and efferent arterioles (EFF) in vivo, and further evaluated whether ACEI-stimulated bradykinin activity differed in superficial (SP) and juxtamedullary nephrons (JM). Arterioles of canine kidneys were visualized with an intravital charge-coupled device camera microscope. E4177 (an angiotensin receptor antagonist, 30 microg/kg) dilated AFF and EFF in SP (15 +/- 3% and 19 +/- 5%) and JM (15 +/- 3% and 18 +/- 4%). Subsequently, cilazaprilat (30 microg/kg) caused further dilation of both AFF (29 +/- 4%) and EFF (36 +/- 4%) in JM, whereas in SP it dilated only EFF (29 +/-3%). Similarly, in the presence of E4177, cilazaprilat caused further increases in sodium excretion. This cilazaprilat-induced vasodilation and natriuresis was abolished by a bradykinin antagonist (N(alpha)-adamantaneacetyl-D-Arg-[Hyp3,Thi5,8,D-Phe7]b radykinin). In parallel with these results, cilazaprilat increased renal bradykinin content, more greatly in the medulla than in the cortex (5.7 +/- 0.4 versus 4.6 +/- 0.1 ng/g). Similarly, cilazaprilat elicited greater bradykinin-dependent increases of nitrite/nitrate in the medulla. In conclusion, zonal heterogeneity in renal bradykinin/nitric oxide levels and segmental differences in reactivity to bradykinin contribute to the diverse responsiveness of renal AFF and EFF to ACEI. ACEI-enhanced kinin action would participate in the amelioration of glomerular hemodynamics and renal sodium excretion by ACEI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Generation of intestinal T cells from progenitors residing in gut cryptopatches.

Cryptopatches (CPs) are part of the murine intestinal immune compartment. Cells isolated from CPs of the small intestine that were c-kit positive (c-kit+) but lineage markers negative (Lin-) gave rise to T cell receptor (TCR) alphabeta and TCR gammadelta intestinal intraepithelial T cells after in vivo transfer or tissue engraftment into severe combined immunodeficient mice. In contrast, cells from Peyer's patches and mesenteric lymph nodes, which belong in the same intestinal immune compartment but lack c-kit+Lin- cells, failed to do so. These findings and results of electron microscopic analysis provide evidence of a local intestinal T cell precursor that develops in the CPs.

Animals↗
PubMed1998

Synovial fluid cytokines and proteinases as markers of temporomandibular joint disease.

PURPOSE: In this article, biochemical markers in the synovial fluid (SF) for detecting intraarticular inflammation and early cartilage degradation of the temporomandibular joint (TMJ) disease were examined. PATIENTS AND METHODS: SF was obtained from 25 TMJs in 22 patients with internal derangement (ID) or osteoarthritis (TMJ-OA), 15 asymptomatic TMJs in 11 normal volunteers, and 10 osteoarthritic knee joints (KNEE-OA). Cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA), and the proteinase activities were detected by enzymography. RESULTS: SF from TMJs with ID and OA showed higher (P < .05) levels (330.1 +/- 347.7 pg/100 microg SF protein) of IL-1beta than the asymptomatic control TMJs (76.7 +/- 95.3 pg/100 microg of SF protein). SF from TMJs with OA contained significantly (P < .05) higher levels of IL-1beta (531.8 +/- 379.6 pg/100 microg of SF protein) and IL-6 (979 +/- 552 pg/100 microg SF protein) than those with ID (IL-1beta: 216.7 +/- 280.1 pg, IL-6: 293 +/- 434 pg). Two matrix metalloproteinases (MMPs) with gelatinolytic activities at 92 kDa and 72 kDa were consistently detected in both the TMJ-SF (either normal or disease) and SF from KNEE-OA. Also detected were weak bands with molecular weight of 83 and 66 kDa. These bands were clearly shown, particularly in knee joints with advanced stages of OA. Western blot analysis delineated that these were active forms of MMP-9 (83 kDa) and MMP-2 (66 kDa). The same bands were also detected in TMJs with OA that showed high levels of IL-1beta and IL-6. CONCLUSION: These findings suggest that concomitant increases in the levels of cytokines (IL-1 and IL-6) and active forms of MMPs could be potential catabolic markers for cartilage degradation in the TMJ.

Adolescent↗
PubMed1998

Intra-articular levels of prostaglandin E2, hyaluronic acid, and chondroitin-4 and -6 sulfates in the temporomandibular joint synovial fluid of patients with internal derangement.

PURPOSE: This study was conducted to measure the intra-articular levels of prostaglandin E2 (PGE2), hyaluronic acid, and chondroitin-4 and -6 sulfate in patients with temporomandibular joint (TMJ) internal derangement involving a closed lock, and to see if these levels correlate with the clinical or arthroscopic findings. PATIENTS AND METHODS: Fifteen female patients (16 joints) with a mean age of 36.7 years were diagnosed as having a closed lock by clinical examination and diagnostic MR imaging. The patient's subjective pain was assessed by a visual analog scale (VAS) and a pain questionnaire (pain score), and the interincisal opening was measured. TMJ aspirates were obtained by washing of the joint with saline containing vitamin B12 as a marker for calibration of data. The samples were assayed for PGE2 with a radioimmunoassay, and the concentrations of unsaturated disaccaride isomers of hyaluronic acid (delta di-HA), chondroitin-4 sulfate (delta di-4S), and chondroitin-6 sulfate (delta di-6S) were measured by high-performance liquid chromatography. Immediately after collection of the synovial aspirates, diagnostic arthroscopy was performed on all but three joints to evaluate the severity of synovitis and cartilage degeneration. The degree of arthroscopic pathology was scored quantitatively. Intra-articular levels of PGE2, delta di-HA(HA), delta di-4S(C4S), and delta di-6S(C6S) were compared with patient's age, mouth opening, VAS rating, pain scores, and arthroscopic scores for synovitis and cartilage degeneration. RESULTS: The PGE2 level did not correlate with the clinical or arthroscopic parameters. HA had a weak correlation with mouth opening (0.54). C4S and C6S were correlated with arthroscopic scores of TMJ degeneration (0.97, 0.89) and with age (0.75, 0.62). The ratio of C4S and C6S to HA was also correlated with the arthroscopic indices of degeneration (0.93, 0.8) and PGE2 level (0.74, 0.69), but not with age. CONCLUSION: The PGE2 level in the TMJ synovial fluid does not specifically reflect the intensity of pain or synovitis, but the detection of high concentrations of C4S and C6S, compared with the amount of HA, is a possible marker of proteoglycan degradation in the TMJ.

Adolescent↗
PubMed1998

Glycosaminoglycan components in temporomandibular joint synovial fluid as markers of joint pathology.

PURPOSE: This study investigated the correlation between temporomandibular joint (TMJ) disease and the composition of glycosaminoglycans (GAGs) components in the synovial fluid (SF). MATERIALS AND METHODS: Synovial fluid (SF) was obtained from 30 TMJs of 28 female patients diagnosed as having a displaced disc with reduction (WR) (seven joints), a displaced disc without reduction (WOR) (13 joints), osteoarthritis (OA) (five joints), or rheumatoid arthritis (RA) (five joints) by MR imaging and clinical examination. After the SF was directly aspirated, It was digested with chondroitinase ABC and hyaluronidase, and the concentration of unsaturated disaccharide isomers of chondroitin 6-sulfate (delta di-6S), chondroitin 4-sulfate (delta di-4S) and hyaluronic acid (delta di-HA) were measured by high-performance liquid chromatography (HPLC) combined with fluorometry. The ratio of delta di-6S or delta di-4S to delta di-HA, and delta di-6S to delta di-4S, were calculated. RESULTS: There were no significant differences in concentrations of delta di-6S, delta di-4S, or delta di-HA among the groups. The ratio of delta di-6S to delta di-4S was 2.7 +/- 1.4 in OA, 2.6 +/- 0.9 in joints with WOR, 2.9 +/- 1.2 in joints with WR, and 1.3 +/- 0.4 in RA synovial fluid. Differences in the delta di-6S: delta di-4S ratio between RA and the other conditions were statistically significant (P < .05). CONCLUSION: These results suggest that the delta di-6S:delta di-4S ratio in the synovial fluid of the TMJ reflects the proteoglycan metabolism of the joint tissues, particularly of the articular cartilage and synovial tissue. This ratio could be used to diagnose joint diseases and to predict articular cartilage destruction or synovial proliferation caused by these diseases.

Adult↗
PubMed1998

Identification of matrix metalloproteinases (MMPs) in synovial fluid from patients with temporomandibular disorder.

Proteolytic enzymes with gelatinolytic activity in the synovial fluid (SF) of temporomandibular joint (TMJ) arthropathies were assayed by gelatin-impregnated gel enzymography. SF samples were collected from 10 TMJs in patients with closed lock (CL) condition and 5 TMJs from asymptomatic healthy volunteers. Two proteinases with gelatinolytic activities at 92 kDa and 72 kDa were detected in both the normal and the diseased TMJs. Also detected were weak bands at molecular weights of 83 kDa and 66 kDa. All of these proteinase activities were inhibited by EDTA and tissue inhibitor of metalloproteinases (TIMP), required Ca2+ for activation, and were detected with gelatin but not casein as substrate, suggesting that these enzymes were matrix metalloproteinases (MMPs). The 72 kDa and 66 kDa bands further reacted with anti-MMP-2 antibody by Western blot analysis, and the proteinases in the TMJ-SF could cleave type IV collagen in vitro without any activation. These four activities identified by enzymography were, therefore, identified as 92 kDa-gelatinase (proMMP-9), 83 kDa-gelatinase (active MMP-9), 72 kDa-gelatinase (proMMP-2) and 66 kDa-gelatinase (active MMP-2). Densitometric analyses of these bands revealed higher levels of the active form of MMP-9 in the CL patients compared to controls. These findings suggest that MMP-2 and -9 could be dominant proteinases in the TMJ-SF and possibly reflect TMJ pathology.

Adolescent↗
PubMed1997

Interleukin 1 beta and stromelysin (MMP3) activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint.

PURPOSE: This study investigated the early signs of synovitis and cartilage degradation by means of synovial fluid analysis in temporomandibular joints (TMJs) with internal derangement (closed lock) or osteoarthritis (OA). PATIENTS AND METHODS: Synovial fluid was obtained from 25 TMJs in 22 patients diagnosed with closed lock and from 15 asymptomatic TMJs of 12 normal controls. IL-1 beta concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and proteinase activity was detected by means of gelatin enzymography. RESULTS: Nine of the 25 TMJs with closed lock (CL group) exhibited osteolytic changes on the surface of the condyle. TMJs in the normal control group did not show any bony changes. Mean IL-1 beta concentration in the synovial fluid (SF) protein in the CL group was 330.1 +/- 347.7 pg per 100 micrograms protein, which was significantly higher than in the normal control (76.7 +/- 95.3 pg/100 micrograms SF-protein). Synovial fluid from the TMJs with osteolytic changes contained higher levels of IL-1 beta (531.8 +/- 379.6 pg/100 micrograms SF-protein) than those without bony changes (216.7 +/- 280.1 pg/100 micrograms SF-protein). Matrix metalloproteinase (MMP) activity with a molecular weight of 50 kd (stromelysin or MMP3) was detected in a highly augmented form in two synovial fluid samples of seven closed lock patients. CONCLUSION: The results suggest that IL-1 beta levels in synovial fluid of the TMJ have a positive correlation with OA change. The MMP3 activity detected was greatly increased in patients with cartilage degradation. These findings suggest that both changes may be important markers of early bone deterioration in TMJs that are undetectable by radiograph imaging.

Adolescent↗
PubMed1997

Immunohistochemical demonstration of bcl-2 protein in ameloblastoma.

The bcl-2 gene is known through its product, bcl-2 protein, which prevents apoptosis, and also by its expression in development, especially in sites characterized by epithelial-mesenchymal interactions. In the developing tooth germ, bcl-2-protein is expressed in the epithelial component. In this study, we examined the expression of bcl-2 protein immunohistochemically in 25 ameloblastomas using a monoclonal antibody against anti-human bcl-2 oncoprotein. In all 25 cases, bcl-2 protein was found mainly in the outer layer of tumor cells, whereas the inner cells (stellate reticulum-like cells and squamoid cells) were negative. The bcl-2 protein is therefore thought to play a role in maintaining the stem-cell population in the peripheral layers of the tumor nests from which proliferating cells can be recruited.

Adolescent↗
PubMed1997

Role of kinin and renal ANG II blockade in acute effects of ACE inhibitors in low-renin hypertension.

In conscious deoxycorticosterone acetate (DOCA) salt-hypertensive dogs, the angiotensin-converting enzyme (ACE) inhibitors captopril and imidaprilat significantly decreased mean arterial pressure (MAP) and significantly increased urine flow rate, effective renal plasma flow (ERPF), glomerular filtration rate, and urinary sodium excretion. However, the angiotensin type 1 (AT1) receptor antagonist losartan caused a significant increase only in urinary sodium excretion without significant changes in MAP, urine flow rate, ERPF, and glomerular filtration rate. Simultaneous infusion of a bradykinin receptor antagonist inhibited the ACE inhibitor-induced reduction in MAP and increase in ERPF. DOCA salt treatment markedly suppressed plasma angiotensin II (ANG II) concentration (P < 0.001), although it decreased renal ANG II content only slightly (P < 0.05). Comparison of the expression of renal AT1 receptor mRNA in control kidneys with that in DOCA salt-hypertensive kidneys revealed no significant change. These results suggest that, in low-renin hypertension, inhibition of the relatively maintained ANG II production in the kidney participates in the natriuretic action of ACE inhibitors. However, hypotensive and other renal effects are mainly due to the action of bradykinin.

Angiotensin II↗
PubMed1997

Role of angiotensin II generated by angiotensin converting enzyme-independent pathways in canine kidney.

Recent studies have provided evidence of angiotensin converting enzyme (ACE)-independent angiotensin (Ang) II formation in tissue renin-angiotensin systems. We studied the effects of Ang II generated by ACE-independent pathways on renal hemodynamics. We used a synthetic peptide, [Pro11, D-Ala12]-Ang I (S), which yields Ang II by chymase, but not by ACE. Infusion of Ang I into a renal artery caused a decrease in renal blood flow, and reciprocally an increase in mean arterial pressure. Infusion of S (1 nmol/kg) caused a decrease in renal blood flow (-20%), but a larger dose was needed to increase mean arterial pressure. Studies with an intravital needle-probe CCD camera revealed that the Ang I infusion induced dose-dependent vasoconstriction of afferent and efferent arterioles (49% and 54%, respectively at 1 nmol/kg). In contrast, infusion of S elicited only 30% constriction of these vessels at a dose of 1 nmol/kg and induced no further constriction at higher doses, indicating that different segments of renal vessels responded in different fashions to Ang II formed via ACE-independent pathways. These vasoconstrictions were abolished by an angiotensin II receptor (AT-1) antagonist. Enzymatic assays using reverse-phase HPLC revealed that the ACE-dependent pathway was predominant in the rena1 cortex (approximately 80%). We also determined Ang II concentrations in renal cortex specimens obtained by needle biopsy. Intrarenal S infusion (10 nmol/kg) increased plasma and renal Ang II concentrations to 160% and 710% of the respective baseline levels. This study provides in vivo evidence of ACE-independent Ang II formation in renal tissue and suggests that this locally-formed Ang II influences the renal circulation in a paracrine fashion.

Angiotensin II↗
PubMed1996

Role of adenosine in the renal responses to contrast medium.

Despite the development of non-ionic radiographic contrast media (CM), CM-induced nephropathy is a clinically important problem in patients with pre-existing renal insufficiency. We examined the effects of non-ionic CM (iohexol) on renal function in conscious dogs with and without renal insufficiency, and evaluated the effects of a non-selective (theophylline), an A1 selective (KW-3902), and an A2 selective adenosine antagonist (KF17837) on the renal responses to CM. In sham-operated group, iohexol (2 ml/kg/min for 3 min) increased effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), whereas in renal insufficiency group (with subtotal nephrectomy), following transient increases in ERPF and GFR, CM markedly decreased ERPF (-46.5 +/- 6.7%) and GFR (-51.2 +/- 7.1%). In sham-operated group, theophylline and KF17837 markedly attenuated CM-induced increases in ERPF and GFR, while KW-3902 had no effects on CM-induced increases in ERPF or GFR. In renal insufficiency group, initial increases in ERPF and GFR were blunted by theophylline and KF17837. In contrast, the subsequent decreases in ERPF and GFR were attenuated by theophylline (% delta ERPF, -12.2 +/- 3.2% vs. -46.6 +/- 6.7%, P < 0.01; % delta GFR, 4.3 +/- 2.5% vs. -51.0 +/- 7.1%, P < 0.01), and were completely prevented by KW-3902 (% delta ERPF, 10.8 +/- 2.9%; % delta GFR, 23.8 +/- 4.4%), whereas KF17837 aggravated ERPF (-73.3 +/- 5.3%) and GFR (-78.4 +/- 5.3%). These data indicate that in normal renal function, iohexol elicits renal vasodilation by activating mainly the adenosine A2 receptors. In contrast, in impaired renal function, CM induces both A2 and A1 activation; the former is associated with the initial renal vasodilation, while the latter is responsible for the sustained aggravation of renal hemodynamics.

Adenosine↗
PubMed1995

Efficient isolation of mutant antigen presenting cell lines by functional selection using T cell clones.

An efficient method for the isolation of mutant antigen-presenting cell (APC) lines is described. When mixtures of transfectant APC lines TA beta z (that express A beta z/A alpha d MHC class II molecules) and hypothetical variant APC lines TA beta d (that express A beta d/A alpha d class II molecules) were cultured with and selected by autoreactive A beta z/A alpha d-restricted T cell clones, the percentage of TA beta d APC lines increased from less than 1% of the original APC mixtures to almost 100% after several cycles of selection. This increase of hypothetical variant was shown to be due to the formation of aggregates of wild-type TA beta z APC lines with A beta z/A alpha d-restricted autoreactive T cell clones that results in the inhibition of proliferation and probably killing of TA beta z APC lines. Based on this, ethyl methane sulfonate (EMS)-treated TA beta z APC lines or B-B hybridoma APC lines MW4 (that express A beta z/A alpha d and A beta z/A alpha z class II molecules) were cultured with and selected by A beta z/A alpha d-restricted autoreactive T cell clones to obtain mutant APC lines that escaped the recognition by T cell clones. After cloning, about 43% of clones examined lost the ability to stimulate T cell clones with concomitant loss of class II molecule expression. Less than 1% showed loss of stimulatory activity against T cell clones in spite of the expression of normal amounts of class II molecules. Initial analysis revealed that they include APC mutant lines with (1) altered MHC class II sequences, (2) loss of adhesion molecule expression and (3) possible impairment of the peptide loading. The method described here may provide a variety of mutant APC lines that are useful for the analysis of antigen processing and presentation pathways as well as of class II structure for T cell stimulation.

Animals↗
PubMed1995

Glucocorticoid-induced hypertension in the elderly. Relation to serum calcium and family history of essential hypertension.

To explore the syndrome of glucocorticoid-induced hypertension in the elderly, we analyzed the clinical findings from 35 patients aged more than 65 years (12 men, 23 women) who received glucocorticoid therapy. Resting blood pressures (BP) were less than 140/90 mm Hg before glucocorticoid therapy, and patients were apparently disease-free apart from the condition for which glucocorticoid therapy was prescribed. Glucocorticoid-induced hypertension is defined as systolic BP more than 160 mm Hg and/or diastolic BP more than 95 mm Hg after glucocorticoid administration. Glucocorticoid-induced hypertension was seen in 13 patients (37.1%); all patients with hypertension [steroid (glucocorticoid)-induced hypertension (SH(+)) group] received more than 20 mg of prednisolone daily, and BP rose rapidly within a week of commencing glucocorticoid administration. The SH(+) group did not differ significantly in terms of age, heart rate, blood count, plasma biochemistry, plasma renin activity, plasma aldosterone, routine urinalysis, or urinary electrolytes from patients who did not show hypertension [SH(-) group]. However, serum total calcium concentrations were significantly lower in the SH(+) group both before and after 2 weeks of glucocorticoid therapy than in the SH(-) group. Furthermore, the SH(+) group showed a significantly higher percentage of patients with a positive family history of essential hypertension than the SH(-) group. In conclusion, although the detailed mechanisms are as yet uncertain, glucocorticoid-induced hypertension occurs often in elderly patients, and is more common in patients with total serum calcium concentrations lower than the normal range, and/or in those with positive family history of essential hypertension.

Aged↗
PubMed1994

Interleukin-2 (IL-2) production by human B-cell line.

A human B-cell line (Hairy-BM) constitutively secreting interleukin-2 (IL-2) was established from tumor tissue resected surgically from a patient with breast cancer. Hairy-BM was found to be 100% CD20+, 98% surface immunoglobulin (sIg) G+, 98% sIg kappa chain+, 100% HLA-DR+, 94% IL-2 receptor (IL-2R alpha), 98% IL-2R beta, and devoid of T-cell, monocyte, and natural killer cell surface antigens. The B-cell origin of Hairy-BM was also confirmed by clonally rearranged Ig heavy- and Ig light-chain genes. The growth of Hairy-BM expressing IL-2R was promoted by recombinant IL-2 (rIL-2) and anti-CD25 antibody significantly blocked the growth enhancement. IL-2 secretion from Hairy-BM was confirmed by radioimmunoassay. By using a sensitive polymerase chain reaction technique, we demonstrated that Hairy-BM expressed IL-2 mRNA, IL-2R alpha mRNA, and IL-2R beta mRNA. These findings indicate that certain B-cells not only produce, but also respond to IL-2 in an autocrine fashion with increased proliferation.

B-Lymphocytes↗
PubMed1994

Increased proliferation of a human breast carcinoma cell line by recombinant interleukin-2.

Two adenocarcinoma cell lines, Breast M25-SF and Breast M, were established from tumor tissue resected surgically from a patient with breast cancer. One, Breast M25-SF, expresses interleukin-2 receptor (IL-2R) on the cell surface and the other, Breast M does not. The effects of recombinant interleukin-2 (rIL-2) on the proliferation of these cell lines were investigated. The growth of Breast M25-SF was significantly promoted by rIL-2 ranging from 1.25 U/ml to 640 U/ml. Anti-CD25 (Tac) antibody significantly blocked the growth enhancement of Breast M25-SF by rIL-2. Breast M, however, did not respond to rIL-2. To confirm more directly the promotion of Breast M25-SF growth by rIL-2, cloning of IL-2 responders from parent Breast M25-SF cells was carried out by limiting dilution without feeder cells in 96-well microplates. No colony formation was found in 24 wells without rIL-2. Eleven, 13 and 6 clones were established from groups of 24 wells containing rIL-2 at 200, 20 and 2 U/ml respectively. All of the clones expressed IL-2R and respond to rIL-2. By using a sensitive polymerase chain reaction technique, we demonstrated that Breast M25-SF but not Breast M expressed IL-2 mRNA, and IL-2 secretion from Breast M25-SF but not Breast M was also confirmed by radioimmunoassay. These findings suggest a role for IL-2 in autocrine support of Breast M25-SF growth. IL-2 may play an important role in the growth control of breast carcinoma cells.

Adenocarcinoma↗
PubMed1994

Inhibition of tumor cell growth by a human B-cell line.

An Adenocarcinoma cell line (Breast-M) and an Epstein-Barr virus (EBV)-infected B-cell line (Hairy-BM) were established from breast tumor tissue. The Hairy-BM was CD20+, CD25 (Tac)+ and surface immunoglobulin (sIg)+. Hairy-BM suppressed the in vitro proliferation of Breast-M in a time- and a dose-dependent manner. The suppression was also found in 5 different human tumor targets showing tumor-Hairy-BM binding, but not; in 2 murine tumor targets showing no significant tumor-Hairy-BM binding. Lytic activity of Hairy-BM was found only against Breast-M.

Adenocarcinoma↗
PubMed1994

Effective induction of human NK cells with OK-432 and further augmentation of their cytolytic function by rIL-2.

Low concentrations of exogenously added recombinant interleukin 2 (rIL-2) were able to augment OK-432-induced natural killer (NK) cell activity. This kind of augmenting effect depended on the dose of rIL-2 and manifested itself only in PBMC stimulated with OK-432 (OK-MC) followed by rIL-2; augmentation did not happen in the reverse order. The existence of CD16+/CD25+ (IL-2 receptor positive; IL-2R+) and CD57+/CD25+ double positive cells which possess NK cell surface markers in OK-MC markedly increased in a long-term culture (12 days). A strong positive correlation was observed between the IL-2-dependent augmentation of NK activity and the quantitative changes in cell populations that possessed NK cell phenotypes. Treatment of the day-12-OK-MC with monoclonal anti-CD56 antibody plus complement could almost completely abrogate the augmented NK cytotoxicity. Furthermore, this augmenting effect was detectable within 4 hr after addition of rIL-2 at single cell level, suggesting that the effect did not require NK cell's DNA synthesis. Thus it was suggested that OK-432 could promote and upregulate the expression of IL-2 receptor (CD25) on CD56+ NK cell populations. Moreover, it was considered that the interaction of low concentration rIL-2 with IL-2 receptors on OK-432-activated NK cells could augment their lytic function.

Antigens, CD↗