Protection of human polymorphonuclear leukocyte function from the deleterious effects of isolation, irradiation, and storage by interferon-gamma and granulocyte-colony-stimulating factor

Granulocyte colony stimulating factor (G-CSF) is well known for its ability to drive the maturation and mobilization of neutrophils. G-CSF also appears to have the potential to activate functions of mature neutrophils, influencing recruitment at sites of inflammation and tissue injury. We investigated the ability of G-CSF to stimulate adhesion of isolated blood neutrophils. G-CSF induced significant adherence to intercellular adhesion molecule (ICAM)-1 that was both macrophage antigen-1 (Mac-1) and leukocyte function-associated antigen-1 dependent. The kinetics of G-CSF-stimulated adhesion to ICAM-1 peaked at 11 min without detectable surface upregulation of Mac-1. This was in marked contrast to chemokines, in which peak activation of adhesion is seen within 1 min of stimulation. In contrast to chemokine-induced adhesion, G-CSF stimulation was not inhibited by pertussis toxin. G-CSF also augmented the attachment of neutrophils to activated human umbilical vein endothelial cells (HUVEC) through specific effects on neutrophils, because HUVEC appear to lack functional G-CSF receptors.

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Continuous subcutaneous injection reduces polymorphonuclear leukocyte activation by granulocyte colony-stimulating factor

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00248.2003 ◽

2004 ◽

Vol 286 (1) ◽

pp. L143-L148 ◽

Cited By ~ 2

Author(s):

Yukio Sato ◽

Yukinobu Goto ◽

Shoko Sato ◽

Shunsuke Endo ◽

Yasunori Sohara

Keyword(s):

Polymorphonuclear Leukocyte ◽

Subcutaneous Injection ◽

Bolus Administration ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Single Bolus ◽

Pmn Elastase ◽

Csf Levels ◽

Pmn Élastase ◽

Stimulating Factor

The use of granulocyte colony stimulating factor (G-CSF) for recovery from neutropenia has been established; however, acute lung injury due to G-CSF-induced polymorphonuclear leukocyte (PMN) activation is a serious complication. This study was designed to compare the activation of PMN with single bolus administration and continuous administration of G-CSF. Healthy volunteers (age 33.8 ± 1.4 yr; n = 6) received a single bolus injection of 50 μm/m2of G-CSF (SI; n = 6) or continuous subcutaneous injection of 50 μm/m2of G-CSF for 24 h (CI; n = 6) and were followed for 48 h. Circulating leukocyte counts, markers of activation on PMN, and circulating levels of G-CSF, IL-6, and PMN elastase were measured. SI rapidly increased serum G-CSF levels, which peaked at 4 h, whereas CI gradually increased G-CSF levels, which remained at a steady level from 8 to 24 h. SI caused a rapid decrease in PMN counts at 0.5 h followed by sustained increase to peak at 12 h. CI gradually increased PMN counts, which peaked at 24 h, but the peak values were not significantly different between the groups. SI-induced activation of PMN, which was characterized by increased expression of CD11b, decreased expression of L-selectin, and increased F-actin content, led to increases in serum IL-6 and PMN elastase level. Such changes were all attenuated with CI ( P < 0.05). We conclude that continuous subcutaneous injection of G-CSF resulted in a marrow response similar to that to a single injection but yielded reduced PMN activation.

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Liposomal amphotericin B (AmBisome) compared with amphotericin B ± FMLP induces significantly less in vitro neutrophil aggregation with granulocyte–colony-stimulating factor/dexamethasone–mobilized allogeneic donor neutrophils

Blood ◽

10.1182/blood.v99.1.384 ◽

2002 ◽

Vol 99 (1) ◽

pp. 384-386 ◽

Cited By ~ 2

Author(s):

Maria Luisa Sulis ◽

Carmella Van de Ven ◽

Theresa Henderson ◽

Lauren Anderson ◽

Mitchell S. Cairo

Keyword(s):

Respiratory Distress ◽

Amphotericin B ◽

Polymorphonuclear Leukocyte ◽

Liposomal Amphotericin ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Neutrophil Aggregation ◽

In Vitro Effects ◽

Stimulating Factor

Concomitant use of allogeneic donor granulocyte transfusions and amphotericin B in febrile neutropenic recipients may be limited by the increased incidence of respiratory distress. In vitro effects of amphotericin B and AmBisome were compared on polymorphonuclear leukocyte (PMN) aggregation from PMNs isolated from granulocyte–colony-stimulating factor (G-CSF)/dexamethasone–mobilized allogeneic donors. Six allogeneic donors were mobilized with G-CSF (600 μg subcutaneously) and dexamethasone (8 mg orally) 12 hours before leukopheresis. AmBisome was associated with significantly less PMN aggregation (100 μM [μg/mL]) (0.33% ± 0.33% vs 54.33% ± 5.82%; P < .001) than amphotericin B. Furthermore, with the addition of the PMN agonist, FMLP, AmBisome was also associated with significantly less aggregation (100 μM [μg/mL]) (18.67% ± 1.45% vs 54.67% ± 2.4%;P < .001). In summary, these studies demonstrate that liposomal amphotericin is associated with significantly less in vitro PMN aggregation than amphotericin B and could possibly be administered concomitantly with mobilized allogeneic PMN infusions.

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