Role of Acetylsalicylic Acid in Cytokine Stimulation of Macrophages in Antibody-Dependent Cellular Cytotoxicity (ADCC)

In addition to the spectrum of biological action already known to be exhibited by acetylsalicylic acid (ASA) as an analgesic, anti-inflammatory and platelet aggregation inhibitor, there is growing evidence of a stimulatory effect on the immune system. ASA has been found to increase the production ofcytokines and to increase the activity of various leukocytes. The action of ASA on the activity of mouse peritoneal macrophages was therefore investigated in the present study. Therapeutically effective concentrations of ASA, which are known to decrease levels of prostaglandins, had neither a stimulating nor an inhibiting influence on antibody-dependent cellular cytotoxicity (ADCC) or on the binding capacity of macrophages with regard to SW 948 tumour cells. Likewise ASA had little or no adverse effect on the capacity of the macrophages for stimulation by interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). Taken together, the immunostimulant effect of ASA shown in the literature as an increased production of interleukin-2 (IL-2) and IFN, could not be confirmed on the basis of the macrophage cytotoxiclty

Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain

The scaffolding protein intersectin 1 plays important roles in clathrin-mediated endocytosis and in the replenishment of release-ready synaptic vesicles (SV). Two splice variants of intersectin's SH3A domain are expressed in the brain, and association of the neuron-specific variant with synapsin I has been shown to enable sustained neurotransmission and to be regulated by an adjacent C-terminal motif. Here, we demonstrate that the ubiquitously expressed short SH3A variant of intersectin 1 interacts with an N-terminal intramolecular sequence that operates synergistically with the C-terminal motif. NMR spectroscopic investigations show that the five-amino acid insertion into the β strand 2 of the neuronal SH3A variant introduces conformational plasticity incompatible with binding of the N-terminal sequence. The difference in the autoregulatory mechanism of the domain's variants differentially affects its synaptic binding partners, thereby establishing alternative splicing in conjunction with autoinhibitory motif variation as a mechanism to regulate protein interaction networks

Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain

The scaffolding protein intersectin 1 plays important roles in clathrin mediated endocytosis and in the replenishment of release ready synaptic vesicles SV . Two splice variants of intersectin s SH3A domain are expressed in the brain, and association of the neuron specific variant with synapsin I has been shown to enable sustained neurotransmission and to be regulated by an adjacent C terminal motif. Here, we demonstrate that the ubiquitously expressed short SH3A variant of intersectin 1 interacts with an N terminal intramolecular sequence that operates synergistically with the C terminal motif. NMR spectroscopic investigations show that the five amino acid insertion into the amp; 946; strand 2 of the neuronal SH3A variant introduces conformational plasticity incompatible with binding of the N terminal sequence. The difference in the autoregulatory mechanism of the domain s variants differentially affects its synaptic binding partners, thereby establishing alternative splicing in conjunction with autoinhibitory motif variation as a mechanism to regulate protein interaction network