Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

Aspects of leucocyte and fat filtration during cardiac surgery

Na een hartoperatie treden vaak door het hele lichaam ontstekingsreacties op. Door het bloed tijdens de operatie te filteren, lopen patiënten minder risico op beschadigingen in longen, hart en hersenen, ontdekte Hans de Vries. Tijdens een hartoperatie neemt de hart-longmachine een aantal lichaamsfuncties over. Deze machine vormt door zijn grote contactoppervlak met het bloed van de patiënt een enorme prikkel voor stollings- en ontstekingsreacties. De ontstekingen kunnen het hele lichaam treffen en zorgen daar voor weefselbeschadigingen. Een sleutelrol in dit schadelijke proces spelen witte bloedlichaampjes (leukocyten) en vetdeeltjes die tijdens de operatie in de bloedbaan komen. De Vries experimenteerde met twee filters die respectievelijk leukocyten en vetdeeltjes uit het bloed verwijderen. Hij ontdekte dat er minder ontstekingsreacties en weefselbeschadigingen optreden wanneer de leukocyten worden gefilterd uit het restbloed van de hart-longmachine. De patiënten blijken dan na de operatie een betere longfunctie te hebben. Het filter vangt overigens niet alle leukocyten weg; het verwijdert vooral de geactiveerde, ziekmakende witte bloedlichaampjes. Ook een vetdeeltjesfilter zorgt voor minder ontstekingsreacties. Voor de patiënten had dit echter geen merkbare gevolgen. Vermoedelijk laat de effectiviteit van dit filter nog te wensen over.

Intracapillary leucocyte accumulation as a novel antihaemorrhagic mechanism in acute pancreatitis in mice

Background: Pancreatic infiltration by leucocytes represents a hallmark in acute pancreatitis. Although leucocytes play an active role in the pathophysiology of this disease, the relation between leucocyte activation, microvascular injury and haemorrhage has not been adequately addressed.Methods: We investigated intrapancreatic leucocyte migration, leucocyte extravasation and pancreatic microperfusion in different models of oedematous and necrotising acute pancreatitis in lys-EGFP-ki mice using fluorescent imaging and time-lapse intravital microscopy.Results: In contrast to the current paradigm of leucocyte recruitment, the initial event of leucocyte activation in acute pancreatitis was represented through a dose- and time-dependent occlusion of pancreatic capillaries by intraluminally migrating leucocytes. Intracapillary leucocyte accumulation (ILA) resulted in dense filling of almost all capillaries close to the area of inflammation and preceded transvenular leucocyte extravasation. ILA was also initiated by isolated exposure of the pancreas to interleukin 8 or fMLP, demonstrating the causal role of chemotactic stimuli in the induction of ILA. The onset of intracapillary leucocyte accumulation was strongly inhibited in LFA-1-/- and ICAM-1-/- mice, but not in Mac-1-/- mice. Moreover, prevention of intracapillary leucocyte accumulation led to the development of massive capillary haemorrhages and transformed mild pancreatitis into lethal haemorrhagic disease.Conclusions: ILA represents a novel protective and potentially lifesaving mechanism of haemostasis in acute pancreatitis. This process depends on expression of LFA-1 and ICAM-1 and precedes the classical steps of the leucocyte recruitment cascade

Phytohaemagglutinin on maternal and umbilical leukocytes

Almost all the umbilical lymphocytes showed more extensive blast cell formation than that of their mother's lymphocytes with PHA. Pathological conditions of mother in pregnancy and labor such as anemia, gestational toxicosis, difficult labor and asphyxia of babies, inhibited the normal response of both maternal and umbilical lymphocytes to PHA.</p

Demonstration of cellular immunity in chronic myeloid leukaemia using leucocyte migration inhibition assay.

Peripheral blood leucocytes from chronic myeloid leukaemia patients in remission were tested for inhibition of migration in presence of solubilized membrane antigens from leukaemic cells in 15 cases. Eight out of 9 autochthonous combinations (88-8%) and 35/49 allogenic combinations (71-4%) showed inhibition of migration. Antigens prepared from relapse leukaemic cell samples in 4 cases showed inhibition of migration of autochthonous as well as allogeneic remission leucocytes. The same batch of CML antigens inhibited migration of normal leucocytes at the level of 22-2%. The difference between inhibition of migration shown by remission leucocytes and normal leucocytes in presence of CML antigens was statistically significant. Solubilized antigens, similarly prepared from normal leucocytes, showed inhibition of migration of remission leucocytes to the extent of 15% only. The difference between the reactivity of CML remission leucocytes to normal and CML antigens was also statistically significant. No enhancement of migration of remission leucocytes was seen with CML antigens

Prevention of transplant rejection can tolerance be achieved with immunosuppressive treatment?

Successful solid organ transplantation is generally attributed to the increasingly precise ability of drugs to control rejection. However, it was recently shown that a few donor haematolymphoid cells can survive for decades in recipients of successful organ allografts, a phenomenon called microchimaerism. The association for decades of haematolymphoid chimaerism with allograft tolerance in experimental transplantation suggests that immunosuppressive drugs merely create a milieu that enables an allograft and its complement of passenger leucocytes to prime the recipient for graft acceptance. Exploitation of this concept requires a fundamental shift in the classical view of passenger leucocytes only as initiators of rejection. Microchimaerism has taught us that solid organ transplantation involves the transfep-öTEwo3öTK}r organ systems to the recipient: the allograft parenchyma an-4oHg-4oonor'-4y&eWtolymphoid system in the form of donor stem cells contajfletwit|4Q(Xj pas-4MTger leucocyte compartment. Each has the potential to integral witty-4-4orrespSnping recipient system and carry out normal physiologi|:a£futy-4ijj£jvwlta5irnmunological self definition. Resistance to initial integralen r-4WMjure £als requires some form of immunosuppression, but mainterçad-4 of donor-4Rjraiine system function will depend on renewable supply of cells, v-4Jrf-4Siyi-4jj-4fvided by engrafted progenitors. Successful clinical application willctepcrrtTon the development of low morbidity methods to enhance engraftment of donor haemopoietic stem cells. Adis international Limited All rights reserved

長期間喫煙による気管支唱息,肺気腫の病態的変化

The influence of long-term cigarette smoking on the pathophysiology of chronic respiratory diseases with obstructive ventilatory dysfunction was discussed in patients with asthma and pulmonary emphysema (PE). 1. In patients with asthma, significant differences in the pathophysiology of the disease were observed between smokers and nonsmokers. A positive RAST score against inhalant allergens, bronchial hyperresponsiveness, and LTB4 generation by leucocytes were significantly more increased in smokers than in nonsmokers. The values of FEV1/FVC and OLco were significantly more decreased, and % RV was significantly more increased in smokers than in nonsmokers. 2. In comparison of asthma with PE, IgE-mediated allergy was significantly more increased in smokers with asthma than in nonsmokers with asthma and in smokers with PE. The values of % FEV1, FEVl %, and % OLco were significantly higher in nonsmokers with asthma than in smokers with PE, however, the % OLco and % RV were not significantly different between smokers with asthma and those with PE. The % LAA of the lungs on HRCT was larger in patients with PE than in smokers and nonsmokers with asthma. The results suggest that cigarette smoking influences the pathophysiology of asthma and PE.長期間喫煙による気管支喘息および肺気腫の病態的変化について若干の検討を加えた｡1.気管支嘱喘息に関しては,喫煙例と非喫煙例との間に以下のような病態的特徴に差が見られた｡吸入抗原に対する特異的IgE抗体の陽性率,気道過敏性,白血球のI:TB4産生能はいずれも,喫煙例で非喫煙例に比べ有意の亢進を示した｡また,喫煙例では,非喫煙例に比べ,FEV1%や% DLcoは有意の低下,% RVは有意の増加傾向を示した｡2.喘息と肺気腫の比較では,IgEにmediateされるア レルギー反応は,喘息の非喫煙例や肺気腫(全て喫煙例)に比べ,喘息の喫煙例で有意の亢進が見られた｡% FEVl,FEV1,% DLco値はいずれも喘息の非喫煙例で,肺気腫と比べ有意に高い値を示したが,% DLcoと% RV値には,喘息の喫煙例と肺気腫の間に有意の差は見られなかった｡また,肺のHRCT上の% I.AAは,肺気腫において,喘息の喫煙例,非喫煙例いずれよりも有意に高い値を示した｡以上の結果より,長期間の喫煙が喘息や肺気腫の病態に影響を与えることが示された

気管支喘息患者における白血球ロイコトリエン産生能に対する不飽和脂肪酸食の効果に影響する因子

Dietary supplementation with perilla seed oil, a vegetable oil rich in α -lin- olenic acid, inhibits the generation of leukotrienes(LTs) by leucocytes in patients with bronchial asthma. We examined the factors that affect the suppression of LT generation by leucocytes with perilla seed oil-rich supplementation in patients with asthma, by comparing the clinical features of patients with asthma, whose generation of leukotriene (LT) C4 was suppressed by dietary supplementation with perilla seed oil (n-3 fatty acids) (group A), with those of patients who showed no suppression of LTC4 generation (group B). Group A showed a significant increase in the generation of LTB4 and L TC4 by leucocytes after corn oil-rich supplementation (n-6 fatty acids), and a significant decrease in the generation of LTB4 and LTC4 after perilla seed oil-rich supplementation (n-3 fatty acid). However, this was not observed in group B. The level of serum IgE and peak expiratory flow (PEF) in group A were significantly higher than in group B. Furthermore, the serum levels of LDL-cholesterol, β-lipoprotein and　phospholipid were significantly lower in group A than in group B. These results suggest that the clinical features differ between these two asthmatic populations with respect to suppression of LTB4 and LTC4 generation by n-3 fatty acids in perilla seed oil-rich supplementation.a-リノレン酸の豊富なエゴマ油の食事は気管支喘息患者の白血球ロイコトリエン(LT)産生能を抑制する｡気管支喘息患者の内,エゴマ油食によりLTC4の産生が抑制された群(A群)と抑制されない群(B群)の臨床データを比較することにより,気管支喘息患者の白血球ロイコトリエン産生能に影響する因子を検討した｡A群はコーン油(n-6系脂肪酸)の豊富な食事後,白血LTB4,LTC4の産生能が増加し,エゴマ油(n-3系脂肪酸)の豊富な食事後LTB4,LTC4の産生能が減少した｡これらの変化はB群では認められなかった｡A群のIgE値,ピークフロー(PEF)値はB群に比し,有意に高値であった｡またLDL-コレステロール,β-リポ蛋白,リン脂質はA群ではB群に比し,有意に低値であった｡これらの結果はエゴマ油の豊富な食事のn-3系脂肪酸によるLTB4,LTC4の産生能の抑制に関して2群の気管支喘息患者群間に臨床データの相違があることを示唆している

気管支喘息の臨床分類とその細胞性および液性因子の特徴

Characteristics of each asthma type classified by clinical symptoms and　findings were studied in 72 patients with bronchial asthma. 1. Ventilatory function tests showed that the values of % MMF, % V(50) and % V(25) were significantly lower in patients with bronchiolar obstruction (type II) compared to the values of those with simple bronchoconstriction type (type Ia) and those with bronchoconstriction + hypersecretion (type Ib). 2. The proportion of neutrophils in bronchoalveolar lavage (BAL) fluid was significantly higher in type II than in type Ia and type Ib. Several　patients with type Ib showed higher proportion of BAL eosinophils. 3. The release of LTC(4) from leucocytes was significantly lower in type II compared with type Ia and type Ib. There was no significant difference in the release of histamine and LTB(4) among the three asthma types.気管支喘息72例を対象に,その臨床病態の特徴を,気道炎症性の細胞および化学伝達物質の観察により検討した｡1.気道反応の特徴を換気機能の面から検討すると,II細気管支閉塞型において,MMF,V(50)やV(25)などの小ないし細気管支領域の換気障害を示すパラメーターの値は,Ia型,Ib型に比べ 有意の低下を示した｡2.気道細胞反応では,II型において,他の臨床病型に比べ,BAL液中好中球の出現頻度の有意の増加が観察された(Ia, p<0.001 ; Ib, p<0.01)｡好酸球の出現頻度は,Ib過分泌型において著しい増加傾向を示す症例が見られたが,その平均出現頻度には3病型間に有意の差は見られなかった｡3.好中球からのメジェー夕ー遊離では,ヒスタミン遊離は,Ia単純性気管支撃縮型において最も高い値が示されたが,推計学的には3病型間に有意の差は見られなかった｡ロイコトリエンC(4)では,Ia型においてII型に比べ有意に高い遊離が観察された(p<0.05)｡ロイコトリエンB(4)遊離には,3病型間に差は見られなかった