We investigated the effects of two antimicrobial peptides (AMPs) isolated from Scolopendra subspinipes mutilans on neutrophil activity. Stimulation of mouse neutrophils with the two AMPs elicited chemotactic migration of the cells in a pertussis toxin-sensitive manner. The two AMPs also stimulated activation of ERK and Akt, which contribute to chemotactic migration of neutrophils. We found that...

Hemorrhage results in excessive production of superoxide that is associated with severe lung injury. We examined whether the superoxide dismutase (SOD) mimetic manganese (III) meso-tetrakis (di-N-ethylimidazole) porphyrin (AEOL 10150) could attenuate this lung injury and whether extracellular SOD (EC-SOD) deficient mice would have increased hemorrhageinduced lung injury. Compared to wildtype mi...

Human pregnancy is associated with a mild pro-inflammatory state, characterized by circulatory neutrophil activation. In order to explore the mechanism underlying this alteration, we examined NETosis during normal gestation. Our data indicate that neutrophils exhibit a pro-NETotic state, modulated in a multimodal manner during pregnancy. In general, circulatory granulocyte colony-stimulating fa...

Group B Streptococcus (GBS) is the leading cause of meningitis in newborn infants. Bacterial cell surface appendages, known as pili, have been recently described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA, contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however, the host receptor and the contribution of PilA in central nervous system (CNS) dise...

Neutrophil activation plays an important role in the inflammatory response to Gram-negative bacterial infections. LPS has been shown to be a major mediator of neutrophil activation which is accompanied by an early down-regulation of L-selectin and up-regulation of CD1lb/CD18. In this study, we investigated whether lipoprotein (LP), the most abundant protein in the outer membrane of bacteria fro...

Accumulating in vivo and in vitro evidence supports the hypothesis that antineutrophil cytoplasm autoantibodies (ANCA) with specificity for proteinase 3 (PR3) and myeloperoxidase (MPO) are involved in the pathophysiology of small-vessel vasculitis. The best-described effector function of these autoantibodies is stimulation of neutrophils to produce reactive oxygen species and to release proteol...

Chemotaxis requires precisely coordinated polymerization and depolymerization of the actin cytoskeleton at leading fronts of migrating cells. However, GPCR activation-controlled F-actin depolymerization remains largely elusive. Here, we reveal a novel signaling pathway, including Gαi, PLC, PKCβ, protein kinase D (PKD), and SSH2, in control of cofilin phosphorylation and actin cytoskeletal reorg...

Neutrophils constitutively undergo apoptosis at both normal and inflamed sites: an important process that limits the toxic potential of the neutrophil. However, the signal pathway for neutrophil apoptosis is currently unknown. In this study, we evaluated the role of p38-mitogen-activated protein kinase (MAPK) in the spontaneous apoptosis of neutrophils in vitro. We found that p38-MAPK was const...

Hemorrhage results in excessive production of superoxide that is associated with severe lung injury. We examined whether the superoxide dismutase (SOD) mimetic manganese(III) mesotetrakis (di-N-ethylimidazole) porphyrin (AEOL 10150) could attenuate this lung injury and whether extracellular (EC)-SOD-deficient mice would have increased hemorrhage-induced lung injury. Compared with wild-type mice...

Ischemia-reperfusion injury (IRI) is a common occurrence following myocardial infarction, transplantation, stroke, and trauma that can lead to multiple organ failure, which remains the foremost cause of death in critically ill patients. Current therapeutic strategies for IRI are mainly palliative, and there is an urgent requirement for a therapeutic that could prevent or reverse tissue damage c...