Disease relevance of PNN

• Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation [1].
• Neutrophil-derived hydrogen peroxide (H2O2) is believed to play an important role in the pathogenesis of vascular injury and pulmonary edema [2].
• Previous work has shown that the Pseudomonas-derived protease, pseudomonas elastase (PAE), can modify transferrin to form iron complexes capable of catalyzing the formation of hydroxyl radical (.OH) from neutrophil (PMN)-derived superoxide (.O2-) and hydrogen peroxide (H2O2) [3].
• These data demonstrate that inhibition of neutrophil CD11b/CD18 surface adherence receptor upregulation reduces granulocyte accumulation in myocardium after hypothermic global ischemia, reduces myocyte damage, and improves ventricular systolic function [4].
• Neutrophil integrins (CD11b/CD18) upregulate in response to cardiopulmonary bypass and ischemic stress, and their role in generating postoperative ventricular dysfunction was examined in this study [4].

Psychiatry related information on PNN

• Neutrophil nonoxidative defense mechanisms include several low molecular weight antimicrobial peptides [5].

High impact information on PNN

• We have purified a PtdIns(3,4,5)P3-sensitive activator of Rac from neutrophil cytosol [6].
• P-Rex1 antisense oligonucleotides reduced endogenous P-Rex1 expression and C5a-stimulated reactive oxygen species formation in a neutrophil-like cell line [6].
• EL-246 blocked greater than 95% of lymphocyte adhesion to peripheral lymph node high endothelial venules and greater than 90% of neutrophil adhesion to E-selectin transfectants [7].
• Thus, the nature and regulation of the release mechanism appear to be very similar to that of the mast cell and neutrophil [8].
• Structure-function analyses suggest that the neutrophil chemotactic activity depends critically upon the C-1 to C-12 domain, including the stereochemistry of the 6-,8-,and 10-olefinic bonds and the presence of both hydroxyl groups [9].

Chemical compound and disease context of PNN

• Using this ex vivo model of lung injury, we studied the role of three putative E-selectin ligands, sialyl-Lewis X, Lewis X, and dimeric sialyl-Lewis X, in mediating neutrophil sequestration and pulmonary edema [10].
• Therefore the role of C5a may be just as important as other known leukocytosis factors (fragments from C3, for example) in promoting complement-dependent neutrophil mobilization in response to tissue injury, infections, or extracorporeal blood treatments [11].
• The therapeutic efficacy of the sulfones, dapsone, and sulfoxone in neutrophilic dermatoses may be related to the effects of these drugs on neutrophil function [12].
• Coupling of the guanine nucleotide regulatory protein to chemotactic peptide receptors in neutrophil membranes and its uncoupling by islet-activating protein, pertussis toxin. A possible role of the toxin substrate in Ca2+-mobilizing receptor-mediated signal transduction [13].
• It is concluded that myocardial infarct sizes are neutrophil-mediated postischaemic tissue injury can be reduced by BW755C applied prior to ischaemia [14].

Biological context of PNN

• In this reaction, the neutrophil particles serve only as a source of O2-. Further, the same changes in kinetics (decrease in apparent Km for NADPH) observed previously when granules from phagocytizing rather than resting cells were employed could be mimicked by varying the rate of O2-generation by the model system [15].
• Although the 3' end of the open reading frame of the clone for pinin showed near identity to a partial cDNA isolated for a pig neutrophil phosphoprotein (Bellavite, P., F. Bazzoni, et al. 1990. Biochem. Biophys. Res. Commun. 170:915-922), the remaining sequence demonstrated little homology to known protein sequences [16].
• Neutrophil implications in platelet deposition and vasoconstriction after deep arterial injury by angioplasty in pigs [17].
• An in vivo, in situ model of neonatal cardiac surgery was established in which neutrophil adherence was manipulated by administering NPC 15669 (an inhibitor of neutrophil CD11b/CD18 surface receptor upregulation) [4].
• Anti-idiotype as antibody against the formyl peptide chemotaxis receptor of the neutrophil [18].

Anatomical context of PNN

• A cDNA expression library from pig blood neutrophils was immunoscreened with a rabbit antiserum raised against a 32 kDa neutrophil membrane phosphoprotein [19].
• These findings demonstrate the presence of a Ca pump in the neutrophil plasma membrane, which is active at physiological concentrations of free cytosolic Ca [20].
• Cl- secretion in a model intestinal epithelium induced by a neutrophil-derived secretagogue [21].
• A reconstituted cell-free system showed that both membrane fraction and neutrophil-related cytosolic components were required for the activity. p47-phox and p67-phox were expressed in the cells [22].
• Transmembrane linkage between surface glycoproteins and components of the cytoplasm in neutrophil leukocytes [23].

Associations of PNN with chemical compounds

• Isolation and characterization of a cDNA clone for a novel serine-rich neutrophil protein [19].
• Neutrophil and pancreatic elastase had little or no effect on PGI2 production [24].
• We conclude from these results that it is unnecessary to invoke a manganese-requiring enzyme as a component of the phagocytically stimulated respiratory system of the neutrophil [15].
• Pretreatment of neutrophils with mAbs to sialyl-Lewis X and Lewis X reduced the neutrophil sequestration, as evidenced by 45% and 27% reductions in MPO activity from control levels, respectively [10].
• Neutrophil elastase, cathepsin G, and the combination of PMA and A23187 have previously been suggested to induce endothelial cell oxy-radical generation [25].

Regulatory relationships of PNN

• In conclusion, pretreatment with G-CSF tended to attenuate rather than enhance neutrophil-dependent acute lung responses to endotoxin [26].
• Immunofluorescence analysis showed that beta-catenin and VE-cadherin staining changed from a uniform distribution along the membrane of control cells to a diffuse pattern for both proteins and finger-like projections for beta-catenin in neutrophil-exposed monolayers [27].
• Transferrin induces maturation of neutrophil granulocyte precursors in vitro [28].

Other interactions of PNN

• AMCF-II may represent a new member of the intercrine-alpha family of neutrophil chemoattractants.(ABSTRACT TRUNCATED AT 250 WORDS)[29]
• Significant up-regulation of IL-1beta and TNF-alpha mRNA levels in alveolar macrophages was observed at 24 and 30 h, respectively, compared to those in cells not exposed to soluble neutrophil products [30].
• Porcine spermadhesin PSP-I/PSP-II stimulates macrophages to release a neutrophil chemotactic substance: modulation by mast cells [31].
• In the present study, we have investigated the involvement of macrophages and mast cells in the neutrophil chemotactic activity of PSP-I/PSP-II and the underlying mechanism [31].
• The Leumedin NPC 15669 (a drug that inhibits leukocyte recruitment) and an antibody to intercellular adhesion molecule-1 (ICAM-1) both prevented neutrophil recruitment and goblet cell degranulation, implicating leukocytes in the response [32].

Analytical, diagnostic and therapeutic context of PNN

• Reduction of the leukocyte population during postischemic coronary reperfusion results in decreased neutrophil-mediated tissue injury [4].
• Analysis of wound fluid by acid-urea polyacrylamide gel electrophoresis, Western blot, and bacterial overlay confirmed that the neutrophil-derived protegrins constituted the major stable antimicrobial polypeptide in the wound fluid [33].
• Using AIF affinity chromatography, the radioactive fraction containing six proteins of molecular mass 45, 63, 87, 90 to 105, 145, and 195 Kd was isolated from 125I surface-labeled neutrophil extracts [34].
• Furthermore, in animal models, SB 290157, inhibited neutrophil recruitment in a guinea pig LPS-induced airway neutrophilia model and decreased paw edema in a rat adjuvant-induced arthritis model [35].
• A cytosolic protein essential for activation of the O2(-)-generating system in neutrophil membrane was highly purified from porcine neutrophils using conventional methods and high performance liquid chromatography [36].

References