dinoprost and Vasculitis

The objective of the study was to determine the presence or levels of antibodies (Abs) against caspase-3 and their clinical relevance in systemic sclerosis (SSc). Anti-caspase-3 Ab was examined by enzyme-linked immunosorbent assay and immunoblotting. IgG anti-caspase-3 Ab levels in SSc patients were higher than in normal controls. SSc patients positive for IgG anti-caspase-3 Ab had significantly longer disease duration, more frequent presence of decreased %VC and %DLco, and elevated levels of serum immunoglobulin and erythrocyte sedimentation rates. IgG anti-caspase-3 Ab levels correlated positively with serum IgG levels, renal vascular resistance, and serum levels of 8-isoprostane. Immunoblotting analysis confirmed the presence of anti-caspase-3 Ab in sera from SSc patients. Caspase-3 enzymatic activity was inhibited by IgG isolated from SSc sera containing IgG anti-caspase-3 Ab. These results suggest that autoantibody against caspase-3 is generated in SSc and that this Ab is related to the severity of pulmonary fibrosis, vascular damage, and inflammation.

Topics: Adult; Apoptosis; Autoantibodies; Biomarkers; Caspase 3; Dinoprost; Female; Humans; Immunoglobulin G; Kidney Diseases; Male; Middle Aged; Predictive Value of Tests; Pulmonary Fibrosis; Renal Circulation; Scleroderma, Systemic; Vasculitis

We investigated the role of microparticles in vascular dysfunction of the multisystemic disorder of preeclampsia in women's omental arteries or mouse arteries. Preeclamptic women displayed increased circulating levels of leukocyte- and platelet-derived microparticles compared with healthy pregnant individuals. Microparticles from preeclamptic, but not healthy, pregnant women induced ex vivo vascular hyporeactivity to serotonin in human omental arteries and mouse aortas. Hyporeactivity was reversed by a nitric-oxide (NO) synthase inhibitor and associated with increased NO production. In the presence of a cyclooxygenase (COX)-2 inhibitor, serotonin-mediated contraction was partially reduced in arteries treated with healthy microparticles but was abolished after treatment with preeclamptic microparticles. This was associated with increased 8-isoprostane production. Preeclamptic microparticles induced up-regulation of inducible nitric-oxide synthase and COX-2 expression, evoked nuclear factor-kappaB activation, and enhanced oxidative and nitrosative stress. Interestingly, the microparticles originating most probably from leukocytes were responsible for the COX-2 vasoconstrictor component of preeclamptic microparticles, whereas those of platelet origin were mainly involved in NO release. Moreover, vascular hyporeactivity was observed in arteries taken from mice treated in vivo with preeclamptic microparticles. This study demonstrates pathophysiological relevance and provides a paradoxical effect of preeclamptic microparticles associated with proinflammatory properties on vessels, leading to enhanced NO and superoxide anion levels and counteraction of increased COX-2 metabolites.

Topics: Animals; Aorta; Arteries; Cell Membrane; Cyclooxygenase 2 Inhibitors; Dinoprost; Endothelium, Vascular; Female; Humans; Mice; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress; Pre-Eclampsia; Pregnancy; Prostaglandins; Serotonin; Transcription Factor RelA; Vasculitis; Vasoconstriction

To investigate the expression of cyclo-oxygenases (COX), key enzymes in propagating inflammatory responses by converting arachidonic acid to prostaglandins, in inflammatory demyelinating disorders of the peripheral nervous system (PNS).. Expression and distribution of COX messenger RNA (mRNA) and protein were studied in sural nerve biopsies, serum, and CSF samples from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), or, for comparison, with vasculitic neuropathy (VN), which is a inflammatory nondemyelinating disorder, and noninflammatory neuropathies (NIN) using RT-PCR, immunohistochemistry, and immunoblotting. To confirm functional COX-2 activity, the expression of prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) was evaluated by ELISA ex vivo and in vitro.. Whereas COX-1 expression was unaltered in all investigated groups, a significant upregulation of COX-2 mRNA was detected in sural nerves from patients with GBS, CIDP, or VN but not in control subjects with noninflammatory disorders. Macrophages were identified as its primary cellular source. Increased COX-2 protein levels were detectable in serum and CSF from all patients with GBS and, in smaller numbers only, in samples from patients with CIDP or VN but not from the NIN group studied. Moreover, increased levels of PGE(2) and PGF(2alpha) were measurable in sera from patients with GBS, CIDP, or VN and in cell culture supernatants from in vitro stimulated macrophages, indicative of COX-2 activity.. Cyclo-oxygenase-2, expressed by macrophages, may generate prostaglandins during acute inflammatory demyelination of the peripheral nerve.

Topics: Acute Disease; Cells, Cultured; Cyclooxygenase 1; Cyclooxygenase 2; Demyelinating Diseases; Dinoprost; Dinoprostone; Guillain-Barre Syndrome; Humans; Immunohistochemistry; Inflammation; Isoenzymes; Macrophages; Membrane Proteins; Monocytes; Peripheral Nervous System Diseases; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sural Nerve; Up-Regulation; Vasculitis