A monoclonal antibody-defined membrane antigen complex is required for neutrophil-neutrophil aggregation

We examined the aggregation responses of normal neutrophils treated with the murine monoclonal antibody (MoAb) 60.3. Addition of MoAb 60.3 to normal neutrophils produced dose-dependent inhibition of neutrophil aggregation in response to phorbol myristate acetate, zymosan-activated plasma, and N-formyl-methionylleucylphenylalanine. We conclude that the membrane glycoprotein complex recognized by MoAb 60.3--designated CDw18- -is required for neutrophil-neutrophil aggregation in vitro.     

In vitro exposure to human immunodeficiency virus type 1 induces apoptotic cell death of the factor-dependent TF-1 hematopoietic cell line

In this study, we evaluated the effect of a short-term exposure (2 hours) to two different lymphocytotropic strains of human immunodeficiency virus type 1 (HIV-1; HIVIIIB and ICR-3) on the survival of a factor-dependent CD34+ hematopoietic progenitor cell line (TF-1). At flow cytometry analysis, a significant (P < .05) increase in the frequency of apoptotic cell death was observed in HIV-1-treated TF- 1 cells, supplemented with low doses of either interleukin-3 (IL-3; 0.02 to 1 ng/mL) or granulocyte-macrophage colony-stimulating factor (GM-CSF; 0.02 to 0.2 ng/mL) with respect to mock-treated cells. On the other hand, higher doses of both cytokines or combinations of suboptimal concentrations of IL-3 plus GM-CSF (eg, 0.2, plus 0.2 ng/mL) completely reversed the HIV-1-induced increase of apoptosis. Remarkably, no signs of productive or latent virus replication were ever observed in HIV-1-treated TF-1 cells up to 16 days of liquid culture. In parallel experiments, the in vitro exposure to HIVIIIB induced a significant and progressive increase of apoptotic death in purified bone marrow CD34+ cells, seeded in liquid cultures in the presence of 1 ng/mL IL-3. The HIV-1-induced apoptosis of TF-1 cells was likely triggered by the simple interaction of HIV-1 envelope glycoprotein gp120 with CD4 receptor, which was expressed at a low level on the surface of TF-1 cells. In fact, treatment of TF-1 cells with recombinant gp120 plus a polyclonal anti-gp120 antibody or with anti-CD4 monoclonal antibody plus rabbit antimouse IgG significantly increased the percentage of apoptotic death. These data suggest that HIV-1, and perhaps also free gp120 in the presence of anti-gp120 antibody; could play a direct role in the pathogenesis of peripheral blood cytopenias in acquired immunodeficiency syndrome patients by inducing apoptotic death of hematopoietic progenitor cells without the need of a direct infection.     

Aspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release

The involvement of metabolites of arachidonic acid in platelet-dense granule secretion and secondary platelet-platelet interactions is well characterized. However, their role in heterotypic interactions dependent on alpha-granule secretion is less well understood. Using platelet-surface expression of P-selectin as a marker of alpha-granule secretion, we have shown that: (1) aspirin treatment of platelets at doses that block dense granule secretion does not inhibit alpha-granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for platelet alpha-granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the platelet lipoxygenase inhibitor 5,8,11- eicosatrynoic acid, by itself and with aspirin, did not decrease ADP- induced P-selectin expression. We conclude that platelet alpha-granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.     

General Homeostasis of the Frequency of Circadian Oscillations

Some well-defined statistical regularities characterize the change in period (tau) of cockroach circadian oscillations subjected to a large temperature step. These are explainable in terms of the well-known temperature-compensation (homeostasis) of tau of circadian oscillations. The same regularities are detectable in published data on the effect of several other variables affecting several other circadian oscillations. The proposition is then developed that the temperature-compensation of tau is only a special case of a general homeostatic conservation of the frequency of circadian oscillations in the face of all changes they are likely to encounter in the cell. Such a general homeostasis of tau is a functional prerequisite for an oscillator to function as a useful "clock."     

Differentiation of memory T cells to virus plaque-forming cells and cytotoxic T lymphocytes

The aims of this study were to define the T-cell subpopulation(s) detected by the virus plaque assay, and particularly to determine whether the virus plaque assay could be used to enumerate cytotoxic T lymphocytes. In addition, studies were undertaken to ascertain whether cell proliferation was required for development of cytotoxic effector function and virus plaque formation by these subpopulations. The results of experiments with a secondary mouse mixed lymphocyte culture (MLC) model indicated that 70 percent of virus plaque-forming cells bore the Ly 1 phenotype and 30 percent the Ly 2,3 phenotype. Three lines of evidence suggested that cytotoxic T lymphocytes (CTL) can be detected by this assay: the fact that some virus plaque-forming cells (V-PFC) bear the same Ly phenotype as CTL; the use of an inhibitor of DNA synthesis indicated that proliferating cells could be eliminated with no effect on V-PFC production and cytotoxic activity of the Ly 2,3 cell population; and that infection of primed lymphocyteswith vesicular stomatitis virus before (MLC) stimulation eliminated cytotoxic activity. In primary MLC, development of V-PFC and CTL was completely abolished by cytosine arabinoside. In contrast, in secondary MLC, some CTL and V- PFC were generated by antigenic stimulation in the absence of proliferation. However, the development of both functions became progressively more susceptible to cytosine arabinoside as the time between primary immunization and in vitro boosting is increased. It is suggested that there may be a considerable disparity between the number of existing effector cells at any given time and the cytotoxic potential, i.e. the number of cells capable of being generated by antigenic stimulation.