Activated platelets express IL-1 activity

Suspensions of washed human platelets express IL-1 activity after activation with agents such as thrombin, collagen, ADP, or epinephrine as judged by the ability of the platelet suspensions to support the growth of a T cell line, D10.G4.1, which exhibits a growth requirement for IL-1. Unactivated platelets express little IL-1 activity. The IL-1 activity expressed by activated platelets appears to be entirely associated with the platelet surface. No IL-1 activity was detected in supernatants derived from suspensions of activated platelets. A mAb specific for IL-1 beta inhibited 90% of the activity expressed by thrombin-activated platelets, whereas a mAb specific for IL-1 alpha inhibited approximately 20% of the activity. A control mAb was without an effect. These results indicate that activated platelets express surface-associated IL-1 activity. Platelet surface IL-1 may provide a mechanism for altering in an extremely localized and rapid manner the properties of IL-1 responsive cells with which platelets come in direct contact during processes of inflammation and vessel wall damage.     

Isolation of the fibrinogen-binding region of platelet thrombospondin

Purified platelet thrombospondin binds to immobilized fibrinogen if both Ca++ and Mg++ are present. Digestion of the purified molecule with thermolysin results in a limited number of discrete proteolytic fragments. When such digests are subjected to affinity chromatography on immobilized fibrinogen, only the fragments with Mr of 120,000 and 140,000 are specifically bound and subsequently eluted by the addition of EDTA to the column buffer. Examination by SDS-PAGE under both reducing and nonreducing conditions reveals that the fibrinogen-binding domain is derived from the region of the thrombospondin molecule containing the interchain disulfide bonds. The requirement for Ca++ and Mg++ for optimal binding to fibrinogen is also manifest by the Mr 120,000/140,000 thermolytic fragments.     

Activation of complement by Schistosoma mansoni schistosomula: killing of parasites by the alternative pathway and requirement of IgG for classical pathway activation.

Living Schistosoma mansoni schistosomula incubated with normal chicken, guinea pig, human, and monkey sera were killed after 4 hr contact at 37 degrees C. The following data indicate that this action is dependent on the activation of the alternative complement pathway (AP): a) the inactivity of RB, RD, and zymosan-treated serum against schistosomula; b) the partial activity of RD restored in FD; c) the full effect of the C4-deficient guinea pig, C2-deficient human, and the agammaglobulinemic human sera; d) the consumption of both the AP and FB after the incubation of NHS with schistosomula; e) the detection of C3d breakdown product during the contact of the C2-deficient human serum with these young parasites. Killing by serum was decreased as the immature schistosomes developed and was completely absent against 4-day-old lung schistosomula (LS). In other experiments, it was demonstrated that schistosomula, in the presence of IgG, were able to initiate complement activation also through the classical pathway (CP). However, the CP does not appear to play a role in the schistosomulicidal activity of complement. The in vivo relevance of these observations is considered.     

Dose dependent inhibition of B-16 melanoma growth in vivo by a synthetic analogue of PGE2

Daily intratumor administration of 16,16-dimethyl-PGE2-methyl ester in two different dosages inhibited tumor growth in C57Bl/6J mice bearing subcutaneous B-16 melanomas. The larger dose (20 microgram/day/mouse) produced a 68% decrease in tumor volume, a 69% decrease in tumor weight and a 60% decrease in the number of cells in mitotic phase. The smaller dose (10microgram/day/mouse) was one fifth less effective than the 20microgram dose but produced similar changes. Histological examination of tumors revealed no significant differences either in the inflammatory cell population or the amount of necrosis in the control and di-M-PGE2-treated tumors.     

Simple and convenient method for culturing anaerobic bacteria.

A simple and convenient method for culturing anaerobic bacteria is described. Cultures can be grown in commercially available flasks normally used for preparation of sterile external solutions. A special disposable rubber flask closure maintains anaerobic conditions in the flask after autoclaving. Growth of a variety of anaerobic oral bacteria was comparable to that obtained after anaerobic incubation of broth cultures in Brewer Anaerobic Jars.     

Amino group modification inhibits ristocetin cofactor activity of human von Willebrand factor

Purified von Willebrand factor rapidly loses activity when treated under mild conditions with the highly specific amino group reagent trinitrobenzenesulfonic acid. Greater than 90 percent inhibition of activity is achieved by modification of only 7 percent of the amino groups. Other modifications such as acetylation and succinylation also abolish activity. It is unlikely that the essential rapidly reacting amino groups function simply in an electrostatic manner since modifications such as amidination and methylation which produce derivatives which retain positive charge are also inactive or nearly so.     

The differential effects of PGE on the immune response in normal and immunosuppressed mice

The effect of 16,16-dimethyl-PGE₂-methyl ester (di-M-PGE₂) on humoral and cellular immunoresponsiveness has been compared in normal mice and in mice immunosuppressed by splenectomy and thymectomy plus antithymocyte serum (ATS). Splenectomy resulted in immunosuppression manifested by augmentation of B-16 melanoma growth; this stimulatory effect was reversed by di-M-PGE₂. In animals immunosuppressed by thymectomy plus ATS, di-M-PGE₂ augmented the humoral and cellular immune responses; this was manifested by slowing of the growth of B-16 melanoma and by stimulating the number of plaque-forming cells, hemagglutinin titers, and delayed-hypersensitivity reactions to sheep erythrocytes. In contrast, in normal (nonthymectomized) mice, di-M-PGE₂ was mildly immunosuppressive. Finally, adriamycin-immunosuppressed normal mice and this suppression were reversed by the addition of di-M-PGE₂ to the treatment regimen.