Granule swelling and cleavage of mitogen-activated protein kinases in human neutrophils undergoing apoptosis.

Extracellular signal-regulated kinase and p38 have been shown to be cleaved in human neutrophils undergoing apoptosis induced by tumor necrosis factor-alpha and cycloheximide. However, the cleavage products of these molecules were undetected when apoptotic neutrophils were pretreated with phenylmethylsulfonyl fluoride or disrupted by nitrogen cavitation before preparation of cell lysates. The electron microscopy revealed that granules in apoptotic neutrophils were significantly swollen than those in control cells.

Increased basal phosphorylation of mitogen-activated protein kinases and reduced responsiveness to inflammatory cytokines in neutrophils from patients with rheumatoid arthritis.

Objective: We studied the functions of peripheral blood (PB) and synovial fluid (SF) neutrophils from patients with rheumatoid arthritis (RA), focusing the molecular basis for the activated state and the functional responsiveness of RA neutrophils to inflammatory cytokines.

Methods: Paired samples of PB neutrophils and SF neutrophils from the inflamed knee joint were obtained from 18 RA patients (5 males and 13 females).

Results: RA neutrophils exhibited increased spontaneous superoxide (O2-) release and adherence, increased basal phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase, accelerated spontaneous apoptosis, and enhanced O2- release in response to N-formyl-methionyl-leucyl-phenylalanine as compared with healthy normal PB neutrophils.

Calcium channel blockers suppress cytokine-induced activation of human neutrophils.

Background: Neutrophils, in concert with proinflammatory cytokines, play an important role in the progression of atherosclerosis. Calcium channel blockers are commonly used in the treatment of hypertension, and their pleiotropic effects, other than the lowering of blood pressure, have been recently recognized.

Methods: We studied the effects of various calcium channel blockers (amlodipine, nicardipine, cilnidipine, benidipine, efonidipine, nifedipine, azelnidipine, verapamil, and diltiazem; each being used at 5 and 10 micromol/l) on superoxide (O(2)(-)) release, migration, and signaling pathways in human neutrophils stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumor necrosis factor-alpha (TNF-alpha).

Toll-like receptor agonists stimulate human neutrophil migration via activation of mitogen-activated protein kinases.

Human neutrophil migratory responses to Toll-like receptor (TLR) agonists were studied using videomicroscopy. When challenged with lipopolysaccharide (LPS, TLR4 agonist) or N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine (P3CSK4, TLR2 agonist), neutrophils displayed enhanced motility, which was found to reflect increased random migration but not directed migration (chemotaxis). Enhanced neutrophil motility was detected within 10 min after stimulation with LPS or P3CSK4, and was sustained for more than 80 min.

Neutrophil elastase as a predicting factor for development of acute lung injury.

Objective: To determine whether the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) associated with systemic inflammatory response syndrome (SIRS) can be predicted by the plasma neutrophil elastase level.

Patients And Methods: Patients were sequentially enrolled after obtaining informed consent. Twenty-three adult patients with SIRS were classified into the following groups; SIRS alone (5 patients), Group A of ALI/ARDS with SIRS (9 patients) that did not require mechanical ventilation, and Group B of ALI/ARDS with SIRS (9 patients) that required mechanical ventilation.