摘要:

AbstractThe effect of interleukin 1a (IL‐1a) produced by E. coli‐derived recombinant DNA was evaluated on various parameters of human neutrophil function. IL‐1aalone stimulated neutrophil hydrogen peroxide production in a dose‐dependent manner, but the rate was much lower than that of opsonized zymosan. IL‐1ainduced release of specific granule contents, but not azurophilic granule contents. Cytochalasin B did not augment the rate of release. IL‐1awas chemotactic for neutrophils at the optimal concentrations of 0.1‐10 ng/ml. Pretreatment of the neutrophils with IL‐1aaugmented neutrophil oxygen radical production induced by opsonized zymosan, and this synergistic effect was evident as early as 10 min after IL‐1awas added to the neutrophil culture. Phagocytosis of opsonized particles by neutrophils, and degranulation induced by opsonized zymosan were also enhanced by IL‐1ain a dose‐dependent manner. The present results suggest that IL‐1ais weak as a direct activator of neutrophil function and that IL‐1ain vivo may augment the response of neutrophils to other stimulators such as foreign bodies.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.621

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractA randomized study was performed to observe the effects induced by heparin and a low molecular weight heparin fraction (at different dosages) on the leukocytes of rats in the presence of experimental venous thrombosis. The experimentation was carried out on two series of animals: the first with a ligature of the inferior vena cava inducing the formation of a thrombus, the second without any ligature. The results show that the induction of thrombosis involves: in the blood, an increase of the number leukocytes, principally polymorphonuclear cells; in the thrombi, a significant rise in the total count of leukocytes, here mononuclear cells; the latter number increases with the dosages of the administered drugs.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.628

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractThe present study investigates the mechanisms of the recognition of tumor antigens by L3T4+helper T cells responsible for the generation of Lyt‐2+cytotoxic T lymphocytes (CTL) against a major histocompatibility complex (MHC) Class II (1a) antigen‐negative syngeneic X5563 plasmacytoma. Treatment of X5563‐immunized spleen cells with anti‐L3T4 antibody plus complement (C) diminished the generation of Lyt‐2+anti‐X5563 CTL. Since the contribution of L3T4+cells was completely replaced by the addition of exogenous lymphokines, it was demonstrated that L3T4+cells functioned as helper T cells assisting the generation of anti‐X5563 CTL responses. Elimination of 1a‐positive accessory cells (AC) from X5563‐immunized spleen cells resulted in the abrogation of CTL generation, whereas the addition of exogenous lymphokines to AC‐depleted X5563 immunized spleen cells restored the CTL response. The addition of anti‐self la antibody to the culture also eliminated CTL responses. These observations demonstrated the requirement of 1a‐positive AC for and the involvement of self la antigens in the activation of helper T cells. Moreover, use of tumor cells pretreated with paraformaldehyde to cultures of X5563‐immunized spleen cells or adding back of AC pretreated with chloroquine to cultures of AC‐depleted immune spleen cells failed to generate CTL responses. Finally, the addition of exogenous lymphokines to the above cultures resulted in appreciable restoration of CTL responses. Taken collectively, these results indicate that L3T4+helper T cells are activated with tumor antigens processed and presented by 1a‐positive AC.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.632

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractHighly purified preparations of cytoplasmic granules from transplantable rat large granular lymphocyte (LGL) tumor lines (rat natural killer (RNK) tumors) were used to immunize rabbits. Antibodies from these animals gave two precipitin lines with granule extracts in Ouchterlony experiments. They reacted with at least four different bands on nitrocellulose blots of SDS gels of LGL granule proteins. By immunofluorescence, specifically adsorbed antigranule antibodies did not recognize LGL or T cell surface antigens but reacted with the cytoplasmic granules in permeabilized RNK tumor cells as well as with normal rat LGL. These same antisera showed little or no reactivity with a panel of other cells, including peripheral blood T cells, thymocytes, macrophages, and EL‐4 tumor cells. F(ab′)2preparations of these antigranule antibodies completely blocked granule‐mediated lysis of both SRBC and nucleated targets, while control F(ab′)2preparations from rabbits immunized with EL‐4 granules or TNP‐KLH showed no significant inhibition of this cytolytic activity at the same antibody concentration. Anti‐granule F(ab′)2preparations specifically inhibited (>75%) rat natural killer (NK) and antibody‐dependent cellular cytotoxicity (ADCC) activities in a dose‐dependent manner but did not effect cytotoxic T cell activity. Pretreatment of either effectors or targets by these antibodies had no effect. Anti‐granule F(ab′)2preparations, at concentrations showing strong inhibition of lysis, did not inhibit the binding of LGL to YAC‐1 or Ab‐coated P815 targets. These results demonstrate that a granule component(s) is necessary for the lytic activity of LGL in both NK and ADCC and provide the first direct evidence that a secretory event involving these granules is part of the lytic process.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.642

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractThe regulatory mechanisms that determine the course of an inflammation induced by an intraperitoneal injection of kaolin were investigated in Listeria‐susceptible CBA and Listeria‐resistant B10 mice. The magnitude of the granulocyte inflammatory response in the peritoneal cavity was high in B10 mice (area under the curve; AUC0‐48 h: 210.9 × 106granulocytes/mouse × h) and lower in CBA mice AUC0‐48 h: 136.8 × 106granulocytes/mouse × h), whereas the reverse was seen for the granulocyte response in the peripheral blood (AUC0‐48 h= 30.5 and 80.7 × 106granulocytes/mouse × h, respectively).With respect to the presence of humoral factors that affect the number of granulocytes in the circulation, sera of both mouse strains sampled 24 h after the kaolin injection had granulocytosis‐inducing effect in CBA recipient mice and did not induce a response in the B10 recipient mice. This divergent sensitivity to serum factors inducing granulocytosis is consistent with the difference in the blood granulocyte response of B10 and CBA mice but does not explain the divergent inflammatory responses in the peritoneal cavity.Computer simulation showed that at least two factors must be taken into consideration to explain the differences in the inflammatory response, i.e., a factor regulating the release of granulocytes from the bone marrow and a factor governing the rate of granulocyte efflux from the site of inflammation.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.653

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractThis investigation was designed to study the effects of relatively low doses of cyclophosphamide (CY) on monocyte function in patients with surgically resected melanoma. Monocytes taken from patients 3 days after receiving 300 mg, 150 mg, or 75 mg CY/m2had decreased interleukin‐1 (IL‐1) production. Production of tumor necrosis factor (TNF)‐like molecules by the same monocytes appeared to be enhanced following 300 mg/m2CY but not after 150 or 75 mg/m2CY. In vitro studies of the direct effects of CY metabolites (mafosfamide and 4‐hydroperoxycyciophosphamide) on human monocytes showed only concomitant decreases in production of IL‐1 and TNF‐like molecules. This occurred at concentrations that did not obviously affect viability, although monocyte spreading was inhibited. No evidence was obtained for in vitro enhancement of TNF‐production. We conclude that CY can affect monocyte function. In vivo it may have both direct effects leading to decreased TNF and IL‐1 production and indirect effects through lymphocytic or haematopoietic systems that activate monocytes to enhanced TNF production. The effects are dose‐dependent. These CY‐induced changes could be responsible in part for some of the alterations in host immunity and tumor resistance that follows administration of the drug.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.659

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractAn implantable chamber consisting of a small reservoir and a perforated segment of silicone tubing has been developed for the collection of leukocytes, fibroblasts, and collagen to analyze inflammatory components and fibroplasia during tissue repair. Using aseptic techniques, these sterile chambers were placed into subcutaneous pockets on the backs of Sprague‐Dawley rats with cells obtained in daily aspirates for 14 d. Differential cell counts were made by using aliquots from the wound fluid. The aspirated cells represented the characteristic, sequential influx of neutrophils, inflammatory macrophages, lymphocytes, activated macrophages, and fibroblasts documented in other models of tissue repair. On d 14, the connective tissue within the lumen of the silicone tube was removed and analyzed for collagen synthesis by measuring3H‐proline incorporation into collagenase‐sensitive protein. This new device for studying wound healing provides a convenient means to harvest cells, fluid, and tissue for cellular, humoral, and biochemical analyses of tissue repair.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.667

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractTumor growth induced a shift in the phenotype of macrophages (MΦ) responsible for factor‐mediated suppression of allogeneic mixed lymphocyte reactions (MLR), and the suppression by tumor‐bearing host (TBH) Mac‐2+MΦ was in part due to production of prostaglandin E2(PGE2). Thioglycollate‐elicited peritoneal MΦ from normal and TBH BALB/c mice were modulated with anti‐Mac‐1, ‐2, or ‐3 monoclonal antibodies (mAb) or depleted with mAb plus complement and cultured in the presence or absence of indomethacin. Culture supernatants derived from mAb plus complement‐depleted Mo were added to the MLR at time of initiation and showed that the suppressor phenotype shifted from Mac‐3+in the normal host to Mac‐2+in the TBH. Mac‐1+MΦ also appeared to be involved in suppression by normal host, but not TBH, MΦ. Loss of MLR suppression (increase in MLR reactivity) correlated with an increase in protein content of the culture supernatants. In an effort to explain both this relationship and the mechanism of MLR suppression, PGE2levels of culture supernatants were determined by radioimmunoassay. Mac‐1+MΦ were involved in the regulation of PGE2production in normal hosts, as both activation and depletion caused an increase in PGE2production. Depletion caused a more dramatic increase in PGE2production than did activation, suggesting that Mac‐1+MΦ had a dampening effect on PGE2production. In contrast, no Mac‐1+MΦ‐mediated regulatory function occurred in the TBH. Mac‐3+MΦ were involved in the regulation of PGE2production in both normal and TBH. Mac‐2+MΦ were the primary producers of PGE2in the TBH, but not in the normal host, as their depletion in the TBH caused a significant loss of PGE2production. Thus, immunosuppression in the TBH was at least partly due to the inability of Mac‐1+and/or Mac‐3+MΦ to control production of PGE2by Mac‐2+MΦ.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.673

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractThe capacity of alveolar macrophages from mice injected with a metastatic Lewis lung carcinoma variant, LLC‐C3, to regulate T‐cell Con A blastogenesis and NK cytotoxicity was studied. During the first 5 days after subcutaneous tumor injection, alveolar macrophages were stimulatory to Con A blastogenesis of normal spleen cells. After 5 days, the alveolar macrophages shifted to become suppressive. The suppressive activity was extensive by day 11, when the primary and metastatic tumor foci were first detectable. The tumor‐bearer alveolar macrophages also suppressed NK cytotoxicity. Alveolar macrophage suppressive activity was sensitive to indomethacin, suggesting a prostaglandin‐dependent suppressor mechanism. Suppression was not mediated by the production of hydrogen peroxide or superoxide, as it was insensitive to catalase or superoxide dismutase. When normal alveolar macrophages were cultured with LLC‐C3 supernatants for over 12 hours, suppressive activity was induced. The results of these studies show that alveolar macrophages of tumor bearers become suppressive with progressive tumor growth and might, thus, facilitate the development of pulmonary metastases.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.682

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractA new application of the Boyden chamber method for the measurement of eosinophil migration, without the need of eosinophil isolation, has been developed. A cell suspension containing a mixture of granulocytes, neutrophils to the greater part, was used. The eosinophils were identified by staining their granules with Chromotrope 2R. The method made it possible to study the migration of eosinophils from normal individuals without eosinophilia. Control experiments demonstrated that the chemotactic and chemokinetic response of eosinophils in the granulocyte mixture was in accordance with the response of isolated eosinophils from the same donor. Normal eosinophils demonstrated a significant chemotactic response to C5f, platelet‐activating factor (PAF), leukotriene B4(LTB4), and f‐meth‐leu‐phe (f‐MLP). Furthermore, PAF was demonstrated to be significantly more eosinophil chemotactic than neutrophil chemotactic.

ISSN:0741-5400    

DOI:10.1002/jlb.42.6.689

出版商:Wiley    

年代:1987

数据来源: WILEY