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Granzyme K (GrK) is a member of a highly conserved group of potent serine proteases specifically found in the secretory granules of cytotoxic T lymphocytes and natural killer cells. Based on the report indicating that inter-alpha inhibitor proteins are the physiological inhibitors of GrK and on previous findings that showed a significant decrease in plasma(More)
Inter-alpha inhibitor protein (IalphaIp) is an endogenous serine protease inhibitor in human plasma. Circulating IalphaIp levels were lower in 51 patients with severe sepsis than in healthy volunteers. Mean levels were 688+/-295 mg/L in patients with severe sepsis who survived (n=32), 486+/-193 mg/L in patients with sepsis who died (n=19), and 872+/-234(More)
Tight junctions (TJ) are multiprotein complexes that function to regulate paracellular transport of molecules through epithelial and endothelial cell layers. Many new tight junction-associated proteins have been identified in the past few years, and their functional roles and interactions have just begun to be elucidated. In this paper, we describe a novel(More)
Extracellular histones are mediators of tissue injury and organ dysfunction; therefore they constitute potential therapeutic targets in sepsis, inflammation, and thrombosis. Histone cytotoxicity in vitro decreases in the presence of plasma. Here, we demonstrate that plasma inter-α inhibitor protein (IAIP) neutralizes the cytotoxic effects of histones and(More)
We have previously shown that increases in blood-brain barrier permeability represent an important component of ischemia-reperfusion related brain injury in the fetus. Pro-inflammatory cytokines could contribute to these abnormalities in blood-brain barrier function. We have generated pharmacological quantities of mouse anti-ovine interleukin-1β monoclonal(More)
Inter-alpha inhibitor proteins (IaIp) are serine proteases inhibitors that modulate endogenous protease activity and have been shown to improve survival in adult models of sepsis. We evaluated the effect of IaIp on survival and systemic responses to sepsis in neonatal mice. Sepsis was induced in 2-d-old mice with lipopolysaccharide (LPS), Escherichia coli,(More)
OBJECTIVES The major forms of human inter-alpha-inhibitor proteins circulating in the plasma are inter-alpha-inhibitor (IalphaI, containing one light peptide chain called bikunin and two heavy chains) and pre-alpha-inhibitor (PalphaI, containing one light and one heavy chain). Although it has been reported that a decrease in IalphaI/PalphaI is correlated(More)
OBJECTIVES To compare inter-alpha inhibitor protein (IaIp) levels in neonates with proven necrotizing enterocolitis (NEC) and neonates with other, nonspecific abdominal disorders. STUDY DESIGN This was a prospective observational study of neonates in the neonatal intensive care unit. NEC was diagnosed according to Bell's staging criteria. The nNeonates in(More)
OBJECTIVE To determine the clinical relevance and prognostic significance of serial measurement of inter-alpha inhibitor proteins (IalphaIp) in severely septic patients. DESIGN A laboratory-based study of serial plasma samples over the first 5 days of severe sepsis from a prospective clinical trial. SETTING Small business and academic medical center(More)
Human inter-α inhibitor proteins are endogenous human plasma proteins that function as serine protease inhibitors. Inter-α inhibitor proteins can block the systemic release of proteases in sepsis and block furin-mediated assembly of protective antigen, an essential stop in the intracellular delivery of the anthrax exotoxins, lethal toxin and edema toxin.(More)