Search

Eleven patients with disseminated midgut carcinoid tumour disease were subjected to hepatic artery embolisation. In six patients, lymphocytosis with a predominance of NK cells occurred and the cytotoxic activity of isolated lymphocytes increased. A relation between NK cell accumulation and subsequent radiological and biochemical response was observed, and it is suggested that anti-tumour mechanisms other than ischaemia may contribute to the therapeutic response in these patients.

Abstract The vasoactive amine histamine is found at high concentrations in the immune and inflammatory tissues. Earlier studies have revealed that histamine regulates the nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent formation of oxygen radicals by phagocytic cells. However, the effects of histamine on intracellular signal transduction mechanisms of relevance to oxidase regulation remain controversial. For this study, we investigated the effects of histamine on NADPH oxidase activity in human neutrophil granulocytes triggered by a lipoxin A[sub 4] receptor agonist [the hexapeptide Trp-Lys-Tyr-Met-Val-Met (WKYMVM), a formyl peptide receptor (FPR) agonist (the chemotactic tripeptide formylmethionyl-leucyl-phenylalanine (fMLF)) and an activator of protein kinase C (phorbol myristate acetate (PMA)]. We report that histamine, acting via H[sub 2] -type histamine receptors (H[sub 2] R), suppresses NADPH oxidase-dependent formation of oxygen radicals induced by WKYMVM and fMLF but not that induced by PMA. Peptide-induced mobilization of granule-localized complement receptor 3 (CR3) was unaffected by histamine suggesting that the inhibition specifically affected NADPH oxidase activation. Our data suggest that histamine downregulates FPRL1- and FPR-induced NADPH oxidase activity upstream of protein kinase C (PKC) and downstream of the separation of the peptide-induced signal into granule secretion and oxidase activation. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cell activity against several types of target cells was found to be subnormal in patients with systemic lupus erythematosus (SLE). Interferon (IFN) boosted the NK activity of cells from SLE patients to a significantly lesser degree than cells from normal controls. The production of IFN after stimulation of blood cells with Sendai virus was significantly decreased in SLE patients with active disease, and in a substantial proportion of the patient the production of phytohaemagglutinin (PHA)-induced IFN was below normal limits. Although the production of virus-induced IFN was clearly inversely correlated to disease activity no such correlation was observed for PHA-induced IFN. Serum levels of both pH2 stable and pH2 labile IFN were significantly higher in SLE patients than in controls. The findings clearly show that SLE is associated with abnormalities in the NK cell-IFN system hut it cannot be stated whether these abnormalities are causally related to the development of disease or are secondary to pathological changes in SLE. [ABSTRACT FROM AUTHOR]

By interaction with monocytes, interleukin-2 (IL-2) suppressed natural killer (NK) cell cytotoxicity (NKCC) of human. Percoll-fractionated, low-density mononuclear cells. The NK-suppressive effect of IL-2 was independent of de novo formation of prostaglandins or protein since it was unaffected by treatment with indomethacin and cycloheximide, respectively. A monoclonal antibody to the p55 (β) moiety of the IL-2 receptor (anti-Tac/anti-CD25) blocked IL-2-induced NKCC suppression but did not affect the NK-enhancing effect of the lymphokine. We conclude that IL-2 exerts a monocyte-dependent, IL-2 β-receptor mediated suppressive influence on human NK cells. [ABSTRACT FROM AUTHOR]

Autologous monocytes irreversibly suppressed Functions of human natural killer (NK) cells including baseline and lymphokine-induced cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC). and interleukin-2 (IL-2)-induced proliferation. The suppression of these NK-cell functions was cell contact-dependent and could be evoked only by purified monocytes, recovered directly from peripheral blood by countercurrent centrifugal elutriation (CCE). The presence of monocytes also induced the disappearance of CD16 and CD56 antigen on CD3 NK cells (CD3 :16+/56+→CD3 /16+ /56 ). By contrast. T-cell proliferation and the expression of CD3 on CD56 T cells were not susceptible to cell contact-mediated suppression by monocytes. The biogenic amine serotonin abrogated monocyte-induced suppression of NK-cell functions as well as down-modulation of CD16;56 NK-cell antigen. Serotonin thus markedly augmented baseline and lymphokine-induced NK-cell cytotoxicity. ADCC. and NK-cell proliferation. and maintained the expression of NK-cell surface antigens in the presence of elutriated monocytes. The effect of serotonin was mediated by 5-HT1A-type serotonin receptors (5-HT1AR) as indicated by mimicry exerted by 5-HT1AR agonists such as 8-OH-DPAT and (+)-ALK. partial antagonism by the 5-HT1AR antagonists pindolol and cyproheptadine. and lack of antagonism by the 5-HT2R antagonist ketanserin or the 5-HT3 R antagonist ondansetron. Our data are suggestive of a cell-to-cell-mediated mechanism by which monocytes down-modulate NK-cell function and phenotype and its serotonergie regulation. [ABSTRACT FROM AUTHOR]

Human peripheral blood monocytes, recovered by counter-current centrifugal elutriation, suppressed interleukin-2 (IL-2)-induced proliferation of autologous lymphocytes, recovered from low density Percoll fractions. Cell sorting experiments, analysis of phenotype of proliferating cells, and removal of defined cellular subsets by complement cytotoxicity revealed that IL-2-induced proliferation was confined to CD3-/16+/56+ natural killer (NK) cells, Monocyte-induced suppression of NK-cell proliferation was completed within 1 h of incubation with monocytes and unrelated lo the formation of prostaglandins or other intermediary factors. The biogenic amine histamine. acting via H2-type histamine receptors (H2R) on monocytes, completely counteracted the monocyte-mediated suppression of IL-2-induced NK-cell proliferation. Our data are suggestive of a H2R-regulated, cell-cell-mediated mechanism by which monocytes down-modulate NK-cell proliferation. [ABSTRACT FROM AUTHOR]

Histamine (10-4to 10-7 M) augmented natural killer cell cytotoxicity (NKCC)of human CD16+. non-T lymphocytes In vitro against the NK-sensitive target cells K562erythroleukaemic. Molt-4 lymphoma, Chang liver cells and against Epstein Barr virus (EBV)-transformed, NK-insensitive Daudi B-lymphoblastoid target ceils by a mechanism of action involving a prostaglandin- and interleukin 1 (IL-l)-independent accessory function of monocytes. No evidence for the production of intermediary, NK-enhancing cytokines by histamine was obtained, indicating a cell-to-cell mediated interaction between monocytes and NK cells as a plausible mechanism of action for the NK-augmenting effect. Monocytes recovered by countercurrent centrifugal elutriation (CCE), but not monocytes recovered by adherence, reconstituted the effect of histamine when added to non-adherent NK cells. The development of NKCC in response to histamine was time-dependent with (i) an induction phase, dependent on the presence of accessory monocytes and ongoing histamine H2-receptor activation (half-maximal response required approximately 30 min treatment of large granular lymphocyte (LGL)-enriched lymphocytes and monocytes with histamine), and (ii) an effector phase. Independent of the presence of monocytes or histamine receptor activation. Histamine-activated mononuclear cells (MNC) continued to exert augmented cytotoxicity for at least 8 h after removal of histamine and monocytes. In .several experiments, histamine-activated NK-effector cells killed > 90%, of the target cells at low baseline NKCC. We suggest that histamine may have a role in non-specific tumour defence by regulating an earlier unrecognized interplay between monocytes and NK cells. [ABSTRACT FROM AUTHOR]

The liver histology in infectious hepatitis or hepatitis A (HA) and serum hepatitis or hepatitis B (HB) is generally described as identical. However, the clinical separation of the two types has been a problem. Today a serological reaction based on the well documented association between hepatitis antigen and HB is of great assistance in the differential diagnosis. The present study of 165 hepatitis cases separated into hepatitis A and B by this test method indicates quantitative differences in the liver histology of the two types. Thus HB was associated with more prominent parenchymal cell damage and Kupffer cell reaction, while intrahepatic cholestasis was found in a significantly higher frequency in cases presumed to represent HA. The presence of intrahepatic cholestasis was associated with higher levels of serum bilirubin but otherwise no correlation was found between liver morphology and biochemical liver tests. The patients included a group of young intravenous amphetamine addicts with HB. No differences of importance were found histologically in addicts and other patients with hepatitis B. [ABSTRACT FROM PUBLISHER]