Studies in fibroblasts, neurons, and platelets have demonstrated the integration of signals from different G protein-coupled receptors (GPCRs) in raising intracellular free Ca(2+). To study signal integration in macrophages, we screened RAW264.7 cells and bone marrow-derived macrophages (BMDM) for their Ca(2+) response to GPCR ligands. We found a synergistic response to complement component 5a ...

During hemodialysis, alternative pathway complement activation leads to pulmonary sequestration of granulocytes, with loss of pulmonary vascular endothelial integrity and, at times, protein-rich pulmonary edema. An in vitro model of this phenomenon was constructed utilizing 51Cr-labeled human umbilical vein endothelial cell cultures. In this system, granulocytes, when exposed to activated compl...

Interactions between complement anaphylatoxins have been investigated in numerous fields; however, their functions during arterial remodeling following injury have not been studied. The inhibitory effect of complement anaphylatoxin C4a on neointima formation induced by C5a following arterial injury was investigated. Mice were subjected to wire-induced endothelial denudation of the femoral arter...

BACKGROUND C5a and its cognate receptor, C5a receptor (C5aR), key elements of complement, are critical modulators of liver immunity and fibrosis. However, the molecular mechanism for the cross talk between complement and liver fibrosis is not well understood. C5a is a potent chemokine regulating migration of cells in the innate immune system. Since activation and migration of hepatic stellate c...

TNF induces hemorrhagic necrosis (HN) when injected into skin exposed to bacterial agents but not when injected into normal skin. In this paper, we present several lines of evidence suggesting that TNF requires the fifth component of complement (C5) to induce HN in skin exposed to bacteria. First, mouse strains that do not have C5 did not develop HN after injection of TNF and bacteria into skin...

Hereditary ATTR V30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by deposition of aberrant transthyretin (TTR). Immunohistochemical examination of sural nerve biopsies in patients with amyloidotic neuropathy show co-aggregation of TTR with several proteins; including apolipoprotein E, serum amyloid P and components of the complement cascade. Complemen...

A low-molecular-weight component of complement, similar to or identical with human C5a, interacts with human polymorphonuclear leukocytes treated with cytochalasin B and provokes extracellular release of lysosomal enzymes from these cells. Enzyme release occurs in the absence of particles and is selective in that it is not accompained by release of cytoplasmic enzymes. Cell viability is not alt...

Abstract Intracellular/autocrine complement proteins have emerged as critical regulators of human Th1 induction and contraction. T cells contain both intracellular C3 C5 activation systems, with C3aR1 C5aR1 stimulation driving cell homeostatic survival normal IFNg production, respectively. Here we demonstrate how the intracellular/autocrine system is regulated by using from first described pati...

Intradermal injection of zymosan into nonsensitized rabbits induces plasma exudation, which is dependent on two mediators: C5a generated in extravascular tissue fluid and a vasodilator prostaglandin generated from substrates localized in cell membranes. This relationship between the complement system and the prostaglandin synthesis system had not previously been explored, and complement activat...

Acute lung injury (ALI) is a devastating disease with an overall mortality rate of 30 to 40%. The coagulation/fibrinolysis system is implicated in the pathogenesis of ALI. Thrombin-activatable fibronolysis inhibitor (TAFI) is an important component of the fibrinolysis system. Recent studies have shown that the active form of TAFI can also regulate inflammatory responses by its ability to inhibi...