Sepsis remains one of the leading causes of death globally, in spite of advanced developments in intensive care and better understandings of pathophysiology related to sepsis. There is no special treatment or drug available for sepsis, currently. Under normal circumstances, neutrophil is a major player in acute infection control. However, during sepsis, the migration abilities and antimicrobial functions of neutrophils are impaired, resulting in a dysregulated immune response. Recent studies have indeed demonstrated that blocking or reversing neutrophil migration and impaired antibacterial function can improve the outcomes in septic animal models. This article systemically synthesized information regarding related factors and signaling involved in the functions of neutrophils in sepsis. This review also discussed the possibility that neutrophils be used as a marker for specific diagnosis and/or prediction of the outcomes of sepsis.
Animals ; Neutrophils/physiology* ; Chemotaxis ; Chemotaxis, Leukocyte ; Sepsis ; Cell Movement

Familial Mediterranean fever (FMF) is an autosomal recessive disease. Although the possibility of multiple immunologic mechanisms have been studied, the actual mechanism is still unresolved. Forty-one patients with FMF (24 males and 17 females with a mean age and disease duration of 17.8 +/- 4.1 and 4.7 +/- 2.3 years, respectively) and 14 healthy controls (10 males and 4 females with a mean age 23.2 +/- 5.1) were involved in the study. A phagotest was studied in both the patients and control groups with a FACScalibur Flow. All patients were in the acute stages of the disease and had not undergone colchicine treatment for 2 months. The percentage blood phagocytic activity of both granulocytes and monocytes were 84.23 +/- 8.76 and 67.28 +/- 10.15 in the patient group and 94.68 +/- 3.24 and 76.23 +/- 5.7 in the control group, respectively. There was no statistically significant difference in the percentage of phagocytic activity of the granulocytes and monocytes between the FMF patients and healthy controls (p > 0.05 and p > 0.05, respectively).
Adolescence ; Adult ; Chemotaxis, Leukocyte ; Familial Mediterranean Fever/immunology* ; Female ; Human ; Male ; Monocytes/immunology ; Neutrophils/immunology ; Phagocytosis*

PURPOSE: Parenteral nutrition is given to infants who tempararily cannot take oral feeding adequately. A lipid emulsion is added to the parenteral to supply essential fatty acids. In neonatal sepsis, elastase from azuropilic granules of the neutrophils is released and rapidly bound to alpha1-Proteinase Inhibitor(alpha1-PI). The lipid emulsion has been noted to markedly inhibit chemotaxis of neutrophils, so we to measured the levels of Elastase-alpha1-Proteinase Inhibitor(E-alpha1-PI) complex to evaluate the effect of intralipid infusions on the neutrophil in newborns with sepsis. METHODS: This study evaluated 8 patients with neonatal sepsis and 12 normal newborns. We measured E-alpha1-PI complex levels in the serum of these patients by ELISA methods. RESULTS: Before infusion with lipid solution, patients with neonatal sepsis had significantly increased levels of E-alpha1-PI complex in comparison with those of vaginally delivered normal newborns. E-alpha1-PI complex levels were significantly decreased after lipid infusions of 0.5g/kg per day, but there was no further significant decrease with higher doses of the infusate. CONCLUSION: We observed the suppression neutrophil elastase levels by lipid infusions in newborn with sepsis. These results suggest that there were no appropriate chemotatic effects of neutrophil in newborn with sepsis. Therefore, we considered whether the lipid infusion was stopped if the newborn with sepsis was infused parenteral nutrition with intralipid.
Chemotaxis ; Enzyme-Linked Immunosorbent Assay ; Fatty Acids, Essential ; Humans ; Infant ; Infant, Newborn* ; Leukocyte Elastase ; Neutrophils ; Pancreatic Elastase* ; Parenteral Nutrition ; Sepsis

Myeloperoxidase (MPO), an iron-containing heme protein localized in the azurophilic granules of neutrophils and in the lysosomes of monocytes, is involved in the killing of several micro-organisms and foreign cells, including bacteria, fungi, viruses, red cells, and malignant or nonmalignant nucleated cells. We experienced a case of myeloperoxidase deficiency in a 10-month-old male patient with recurrent skin abscess. His leukocyte count was 12,340/microliter with 35% neutrophils. Compared with normal control neutrophils, the patient's neutrophils in the peripheral blood showed normal chemotaxis and phagocytic activity, increased respiratory burst activity in the stimulation with PMA, but, revealed the decreased microbial killing activity. These findings were suggestive of neutrophil granular defects such as myeloperoxidase deficiency and other specific granule content deficiency. The patient's neutrophils showed partially decreased MPO activity in the MPO stain.
Abscess ; Bacteria ; Chemotaxis ; Fungi ; Hemeproteins ; Homicide ; Humans ; Infant ; Leukocyte Count ; Lysosomes ; Male ; Monocytes ; Neutrophils* ; Peroxidase* ; Respiratory Burst ; Skin

Through the optimised research by simplex method, authors have found the optimal conditions of ANAE cytichemistry reaction such as the temperature of 37oC, pH=7.98, the time of 1 hour; especially with this method we can reduce the substance by 7-8 times compared other one
Monocytes ; Leukocyte Rolling

Human polymorphonuclear leukocytes (PMN) migrate into tissues in response to chemoattractants, yet it is not known whether this process alters the functional capabilities of the PMN. Using recombinant human interleukin-8 (rHIL-8, 100 ng/ml) as a stimulus, we compared a population of PMN that migrated through a polyvinylpyrrolidone-coated polycarbonate filter containing 8.0 microns diameter pores with PMN stimulated in suspension. PMN were analyzed by flow cytometry according to functional and phenotypic criteria. CD11b/CD16 expression was unaltered by chemotaxis. In contrast, chemotaxis enhanced phagocytosis of E. coli, independent of opsonization with IgG. Similarly, chemotaxis increased baseline hydrogen peroxide production. We conclude that the chemotactic motion of PMN "primes" the cell for increased oxidative burst activity and augments the ability of PMN to ingest bacteria. This increased functional capability is distinct from rHIL-8 stimulation and appears to be independent of complement-and Fc-receptor expression.
Antigens, CD/analysis ; Chemotaxis, Leukocyte/*physiology ; Escherichia coli/immunology ; Humans ; Neutrophils/physiology ; Phagocytosis/physiology ; Phenotype ; Receptors, IgG/analysis ; Respiratory Burst/physiology

The functional immaturity of PMNs is one of the major causes of overwhelming sepsis in newborns. In this study, we observed functions and surface markers of PMNs to investigate what causes the functional immaturity of PMNs in newborns. As results, the percentage of EA rosette forming PMNs (58.5 +/- 15.5%) and the chemotactic movement (0.14 +/- 0.09 mm) of cord blood PMNs were significantly lower than those of adult peripheral blood PMNs (70.8 +/- 9.9%, 0.60 +/- 0.34 mm). Cord blood PMNs showed decreased glass adherence and ADCC activity. The expression of Fc gamma RII or Fc gamma RIII was a little lower than those of adult peripheral blood PMNs, but the expression of Fc gamma RI (43.1 +/- 26.8%) was significantly higher than that of adult peripheral blood PMNs (3.2 +/- 1.8%). There was a significant difference in LFA-1 expression between EA rosette forming PMNs (92.9 +/- 9.1%) and EA rosette non-forming PMNs (25.6 +/- 22.6%). From these results, it is assumed that neonatal PMNs may consist of heterogeneous populations. And the relatively high percentage of EA rosette non-forming PMNs which express a low level of LFA-1 may be responsible for the functional immaturity of cord blood PMNs.
Antibody-Dependent Cell Cytotoxicity ; Cell Adhesion ; Chemotaxis, Leukocyte ; Fetal Blood/*cytology ; Human ; Lymphocyte Function-Associated Antigen-1/*physiology ; Neutrophils/*physiology ; Receptors, IgG/*physiology ; Rosette Formation

BACKGROUNDCC chemokine receptor 3 (CCR3), expressed on some inflammatory cells, is a member of the chemokine receptor family. Its ligand is eotaxin/CCL11. In this research, we studied the expression and function of CCR3 induced by interleukin-2 (IL-2) and interleukin-4 (IL-4) on human germinal centre (GC) B cells.

METHODSCells isolated from human tonsils were stimulated with IL-2 or/and IL-4 followed by bonding with eotaxin/CCL11. Flow cytometry was used to detect expression of CCR3 on GC B cells and apoptosis of GC B cells. Real time quantitative reverse transcription polymerase chain reaction and Northern blot assays were used to analyse the CCR3 mRNA expressed in the GC B cells. Chemotaxis and adhesion assays were used to determine the effect of eotaxin/CCL11 ligand bonded to CCR3 on GC B cells.

RESULTSThere was no CCR3 expression on human freshly isolated GC B cells. The combination IL-2 and IL-4 could upregulate CCR3 mRNA and protein expression on GC B cells. Eotaxin could not induce GC B cell chemotaxis and adhesion but triggered apoptosis of GC B cells.

CONCLUSIONIL-2 and IL-4 together induced expression of CCR3 on GC B cells, and the receptor acted as a death receptor.

Apoptosis ; B-Lymphocytes ; metabolism ; pathology ; Cell Adhesion ; Chemotaxis, Leukocyte ; Germinal Center ; metabolism ; pathology ; Humans ; Interleukin-2 ; pharmacology ; Interleukin-4 ; pharmacology ; RNA, Messenger ; analysis ; Receptors, CCR3 ; Receptors, Chemokine ; genetics

Neutrophils play a key role in innate immunity, and the identification of new stimuli that stimulate neutrophil activity is a very important issue. In this study, we identified three novel peptides by screening a synthetic hexapeptide combinatorial library. The identified peptides GMMWAI, MMHWAM, and MMHWFM caused an increase in intracellular Ca2+ in a concentration-dependent manner via phospholipase C activity in human neutrophils. The three peptides acted specifically on neutrophils and monocytes and not on other non-leukocytic cells. As a physiological characteristic of the peptides, we observed that the three peptides induced chemotactic migration of neutrophils as well as stimulated superoxide anion production. Studying receptor specificity, we observed that two of the peptides (GMMWAI and MMHWFM) acted on formyl peptide receptor (FPR)1 while the other peptide (MMHWAM) acted on FPR2. Since the three novel peptides were specific agonists for FPR1 or FPR2, they might be useful tools to study FPR1- or FPR2-mediated immune response and signaling.
Animals ; Calcium/metabolism ; Cell Line ; Cells, Cultured ; Chemotaxis, Leukocyte/drug effects ; Humans ; Mice ; NIH 3T3 Cells ; Neutrophils/*cytology/*drug effects ; PC12 Cells ; Peptides/*pharmacology ; Rats ; Receptors, Formyl Peptide/agonists

AIMTo study the inhibitory effect of ginkgolide B (BN52021) on the PAF induced changes of chemotaxis of murine peritoneal macrophages and the related polymerization of F-actin.

METHODSChemotaxis assays were performed using a modified 48-well Boyden chamber. Actin polymerization of murine peritoneal macrophages was analyzed by flow cytometry using a specific fluorescent stain.

RESULTSPeritoneal macrophages significantly migrated toward platelet-activating factor (PAF) through a micropore filter; however, in the presence of PAF receptor antagonist BN52021 (0.01 nmol x L(-1) -0.1 micromol x L(-1)), the migration was significantly inhibited. Moreover, BN52021 inhibited the actin polymerization of murine peritoneal macrophages induced by PAF in the presence of Ca2+, but not in Ca2+ -free medium.

CONCLUSIONThe results suggested that preventing polymerization of F-actin may be a pathway by BN52021 to inhibit the chemotaxis of macrophages, and this effect seems to be Ca2+ dependent. The data further indicated that inhibition of PAF induced macrophage chemotaxis is an important mechanism underlying the anti-inflammatory action of BN52021.

Actins ; metabolism ; Animals ; Chemotaxis, Leukocyte ; drug effects ; Diterpenes ; isolation & purification ; pharmacology ; Ginkgo biloba ; chemistry ; Ginkgolides ; Lactones ; isolation & purification ; pharmacology ; Macrophages, Peritoneal ; metabolism ; physiology ; Mice ; Mice, Inbred C57BL ; Plants, Medicinal ; chemistry ; Platelet Activating Factor ; antagonists & inhibitors