Recombinant human granulocytemacrophage colony-stimulating factor induces granule exocytosis from human polymorphonuclear neutrophils

Inflammation ◽  
1990 ◽  
Vol 14 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Robert J. Smith ◽  
James M. Justen ◽  
Laurel M. Sam
Keyword(s):  
Polymorphonuclear Neutrophils ◽  
Colony Stimulating Factor ◽  
Granule Exocytosis ◽  
Stimulating Factor

scholarly journals Effect of granulocyte colony-stimulating factor on the candidacidal activity of polymorphonuclear neutrophils and their collaboration with fluconazole.

1997 ◽  
Vol 41 (7) ◽  
pp. 1575-1578 ◽  
Author(s):  
U Natarajan ◽  
E Brummer ◽  
D A Stevens
Keyword(s):  
Candida Albicans ◽  
Polymorphonuclear Neutrophils ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Fungal Exposure ◽  
Before And After ◽  
Stimulating Factor ◽  
Strain Dependent

The effect of granulocyte colony-stimulating factor (GCSF) treatment of polymorphonuclear neutrophils (PMN) in vitro was studied with respect to their candidacidal activity. The candidacidal activity of PMN was found to be significantly increased when they were pretreated with GCSF. Fluconazole (1 microg/ml) was found to be highly fungistatic (90%) for Candida albicans Sh27 and collaborated with PMN for significantly increased killing. Collaborative killing by PMN significantly increased when they were treated with GCSF before and after fungal exposure. The enhancing activities of GCSF required optimization of the GCSF dose and were thus inoculum and strain dependent.

Antidisialoganglioside/granulocyte macrophage–colony-stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on FcγRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azurophil granule exocytosis

Blood ◽  
2002 ◽  
Vol 99 (11) ◽  
pp. 4166-4173 ◽  
Author(s):  
Leonid S. Metelitsa ◽  
Stephen D. Gillies ◽  
Michael Super ◽  
Hiroyuki Shimada ◽  
C. Patrick Reynolds ◽  
...  
Keyword(s):  
Neuroblastoma Cells ◽  
Colony Stimulating Factor ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Granule Exocytosis ◽  
Gm Csf ◽  
Azurophil Granule ◽  
Macrophage Colony Stimulating Factor ◽  
Calcein Am ◽  
Macrophage Colony ◽  
Stimulating Factor

Polymorphonuclear leukocytes (PMNs) mediate antibody-dependent cellular cytotoxicity (ADCC), which is increased by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to determine whether PMN ADCC also would be increased by the addition of an antibody/GM-CSF fusion protein and whether this would be associated with the up-regulation and activation of Mac-1 (CD11b/CD18) and with azurophil granule exocytosis. ADCC against LA-N-1 human neuroblastoma cells was evaluated with 4-hour calcein acetoxymethyl ester (calcein-AM) microcytotoxicity assay, electron microscopy, and multi-parameter flow cytometry. With the calcein-AM assay, LA-N-1 cell survival was 10%, 55%, and 75% when PMN ADCC was mediated by the antidisialoganglioside (anti-GD2) immunocytokine hu14.18/GM-CSF, by monoclonal antibody (mAb) hu14.18 mixed with GM-CSF, and by hu14.18 alone. Function-blocking mAbs demonstrated that FcγRII and FcγRIII were required for ADCC with hu14.18 alone or mixed with GM-CSF, but that only FcγRII was required for ADCC with hu14.18/GM-CSF. ADCC mediated by hu14.18 and hu14.18/GM-CSF was Mac-1 dependent. Electron microscopy demonstrated the greatest PMN adhesion, spreading, and lysis of targets with hu14.18/GM-CSF. Monoclonal antibodies blocking Mac-1 function allowed the tethering of PMN to targets with hu14.18/GM-CSF but prevented adhesion, spreading, and cytolysis. Flow cytometry showed that hu14.18 with or without GM-CSF and hu14.18/GM-CSF all mediated Mac-1–dependent PMN–target cell conjugate formation but that GM-CSF was required for the highest expression and activation of Mac-1, as evidenced by the mAb24-defined β2-integrin activation epitope. Hu14.18/GM-CSF induced the highest sustained azurophil granule exocytosis, almost exclusively in PMNs with activated Mac-1. Thus, hu14.18/GM-CSF facilitates PMN ADCC against neuroblastoma cells associated with FcγRII and Mac-1–dependent enhanced adhesion and degranulation.

scholarly journals Inescapable Need for Neutrophils as Mediators of Cellular Innate Immunity to Acute Pseudomonas aeruginosa Pneumonia

2009 ◽  
Vol 77 (12) ◽  
pp. 5300-5310 ◽  
Author(s):  
Andrew Y. Koh ◽  
Gregory P. Priebe ◽  
Christopher Ray ◽  
Nico Van Rooijen ◽  
Gerald B. Pier
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Innate Immunity ◽  
Innate Immune System ◽  
Experimental System ◽  
Lung Infection ◽  
Innate Immune ◽  
Polymorphonuclear Neutrophils ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

ABSTRACT Pseudomonas aeruginosa is a leading cause of pneumonia, and many components of the innate immune system have been proposed to exert important effects in preventing lung infection. However, a vigorous experimental system to identify an overriding, key effector mediating innate immunity to lung infection has not been utilized. As many of the important components of innate immunity are involved in recruitment and activation of polymorphonuclear neutrophils (PMNs) to infected tissues, we hypothesized that the cells and factors needed for their proper recruitment to the lung comprised the major mediators of innate immunity. In neutropenic mice, intranasal (i.n.) doses of P. aeruginosa as low as 10 to 100 CFU/mouse produced a fatal lung infection, compared with 107 to >108 CFU for nonneutropenic mice. There was only a very modest increased mortality in mice lacking mature lymphocytes and no increased mortality in mice depleted of alveolar macrophages when administered i.n. P. aeruginosa. Recombinant mouse granulocyte colony-stimulating factor increased survival of neutropenic mice after i.n. P. aeruginosa inoculation. MyD88−/− mice, which cannot recruit PMNs to the lungs, were highly susceptible to fatal P. aeruginosa lung infection, with bacterial doses of <120 CFU being lethal. Activation of a MyD88-independent pathway for PMN recruitment to the lungs in MyD88−/− mice resulted in enhanced protection against P. aeruginosa lung infection. Overall, in the absence of PMNs, mice cannot resist P. aeruginosa lung infection from extremely small bacterial doses. There is an inescapable requirement for local PMN recruitment and activation to mediate innate immunity to P. aeruginosa lung infection.

Reprogramming of human postmitotic neutrophils into macrophages by growth factors

Blood ◽  
2004 ◽  
Vol 103 (8) ◽  
pp. 2973-2980 ◽  
Author(s):  
Hiroto Araki ◽  
Naoyuki Katayama ◽  
Yoshihiro Yamashita ◽  
Hiroyuki Mano ◽  
Atsushi Fujieda ◽  
...  
Keyword(s):  
Cell Population ◽  
Mannose Receptor ◽  
Polymorphonuclear Neutrophils ◽  
Interleukin 4 ◽  
Nonspecific Esterase ◽  
Colony Stimulating Factor ◽  
Ki 67 ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract It is generally recognized that postmitotic neutrophils give rise to polymorphonuclear neutrophils alone. We obtained evidence for a lineage switch of human postmitotic neutrophils into macrophages in culture. When the CD15+CD14- cell population, which predominantly consists of band neutrophils, was cultured with granulocyte macrophage–colony-stimulating factor, tumor necrosis factor-α, interferon-γ, and interleukin-4, and subsequently with macrophage colony-stimulating factor alone, the resultant cells had morphologic, cytochemical, and phenotypic features of macrophages. In contrast to the starting population, they were negative for myeloperoxidase, specific esterase, and lactoferrin, and they up-regulated nonspecific esterase activity and the expression of macrophage colony-stimulating factor receptor, mannose receptor, and HLA-DR. CD15+CD14- cells proceeded to macrophages through the CD15-CD14- cell population. Microarray analysis of gene expression also disclosed the lineage conversion from neutrophils to macrophages. Macrophages derived from CD15+CD14- neutrophils had phagocytic function. Data obtained using 3 different techniques, including Ki-67 staining, bromodeoxyuridine incorporation, and cytoplasmic dye labeling, together with the yield of cells, indicated that the generation of macrophages from CD15+CD14- neutrophils did not result from a contamination of progenitors for macrophages. Our data show that in response to cytokines, postmitotic neutrophils can become macrophages. This may represent another differentiation pathway toward macrophages in human postnatal hematopoiesis. (Blood. 2004;103:2973-2980)

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