[Regulation of human neutrophil oxidative burst by pro- and anti-inflammatory cytokines]. / Régulation de l'explosion oxydative des polynucléaires neutrophiles humains par les cytokines pro- et anti-inflammatoires.

Human polymorphonuclear neutrophils play a key role in host defenses against invading microorganisms. In response to a variety of stimuli, neutrophils release large quantities of superoxide anion (O2.-) in a phenomenon known as the respiratory burst. O2.- is the precursor of potent oxidants, which are essential for bacterial killing and also potentiate inflammatory reactions. Regulation of this production is therefore critical to kill pathogens without inducing tissue injury. Neutrophil production of O2.- is dependent on the respiratory burst oxidase, or NADPH oxidase, a multicomponent enzyme system that catalyzes NADPH-dependent reduction of oxygen to O2.-. NADPH oxidase is activated and regulated by various neutrophil stimuli at infectious or inflammatory sites. Proinflammatory cytokines such as GM-CSF, TNF and IL-8 modulate NADPH oxidase activity through a priming phenomenon. These cytokines induce a very weak oxidative response by PMN but strongly enhance neutrophil release of reactive oxygen species on exposure to a secondary applied stimulus such as bacterial N-formyl peptides. Priming phenomena are involved in normal innate immune defense and in some inflammatory diseases. The mechanisms underlying the priming process are poorly understood, although some studies have suggested that priming with various agonists is regulated at the receptor and post-receptor levels. Resolution of inflammation involves desensitization phenomena and cytokines are involved in this process by various mechanisms. A better understanding of phenomena involved in the regulation of NADPH oxidase could help to develop novel therapeutic agents for inflammatory diseases involving abnormal neutrophil superoxide production.

Priming of phosphatidic acid production by staurosporine in f-Met-Leu-Phe-stimulated human neutrophils--correlation with respiratory burst.

Staurosporine, a microbial alkaloid known as a potent though non specific PKC inhibitor, enhances the production of superoxide anion (respiratory burst) of human polymorphonuclear leukocytes (PMN) stimulated by chemoattractants such as f-Met-Leu-Phe (fMLP). To gain insights into the mechanisms of this priming, we analysed staurosporine effects on formation of second messengers issued from phospholipase D (PLD), i.e., phosphatidic acid (PA) and its dephosphorylated form, diglycerides (DG). PA and DG were measured by two methods, in mass and after the labelling of PMN with a phosphatidylcholine precursor, [3H]-1-O-alkyl-2-lyso-3-phosphatidylcholine. Treatment of labelled PMN with low concentrations of staurosporine (12.5 and 50 nM) which prime respiratory burst had no significant effect on basal amounts of tritiated PA and DG, but potentiated fMLP-mediated formation of [3H]PA and phosphatidylethanol (PEt) pointing to a priming of PLD activity. PA mass in resting PMN increased (approximately 80 +/- 7%) in the presence of high drug concentrations only (250-500 nM), with no change in basal DAG mass. Low staurosporine concentrations (6.25-25 nM) markedly potentiated PA mass formation induced by fMLP and positive correlation (R = 0.95) was found between enhanced superoxide formation and generation of PA but not DG. Furthermore, cytochalasin B, which is known to prime PA production induced by fMLP, synergised the priming of respiratory burst by staurosporine, which further suggests a functional role of PA. In contrast to staurosporine, the more selective PKC inhibitor GF109203X neither stimulated PLD nor primed fMLP-induced PLD or respiratory burst. These data indicate that priming of fMLP-mediated PMN respiratory burst by staurosporine correlates with PA formation. This priming may be linked to alteration of early signalling events upstream of PLD rather than to feedback inhibition of PKC.

Ease of continuous dermal suture removal.

The purpose of this investigation is to identify the synthetic nonabsorbable monofilament suture that requires the lowest forces for removal of continuous dermal sutures. Immediately after wound closure, continuous dermal polypropylene sutures require the lowest suture removal forces. The ease of polypropylene suture removal from continuous dermal skin closure is related to the suture's low surface coefficient of friction.

Some biomechanical considerations of polytetrafluoroethylene sutures.

The biomechanical performance of polytetrafluoroethylene (PTFE) sutures has been compared with that of polypropylene sutures, the standard to which other sutures used in vascular and cardiac surgery are compared. The PTFE is supple and has no plastic memory, while the polypropylene suture is stiff and retains its plastic memory. In addition, the rate of creep encountered in the PTFE suture was significantly less than that of the polypropylene suture. The knotting profiles for knot security for either a square, granny, or surgeon's knot for polypropylene sutures were three throws each. In contrast, knot security with either a square or granny PTFE knot was accomplished with seven throws; six throws were needed for a secure surgeon's knot. The breaking strength of the unknotted and knotted PTFE sutures was approximately one half as great as that for the unknotted and knotted polypropylene sutures. Knot construction significantly reduced the breaking strength of polypropylene sutures but did not alter the breaking strength of PTFE sutures. The percent elongation experienced by both sutures before breakage did not differ significantly. The elasticity, as measured by work recovery, for the polypropylene suture was greater than that for the PTFE suture. On the basis of its unique biomechanical performance characteristics, the PTFE suture should have an important place in vascular and cardiac surgery.