Mechanisms of Tumor Necrosis Factor Alpha-Induced Lymphopenia, Neutropenia, and Biphasic Neutrophilia: A Study of Lymphocyte Recirculation and Hematologic Interactions of TNFα With Endogenous Mediators of Leukocyte Trafficking

Ulich, Thomas R.; Castillo, Juan; Ni, Rong-Xiang; Bikhazi, N.; Calvin, Lyle D.

doi:10.1002/jlb.45.2.155

Cited by 57 publications

(33 citation statements)

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“…No such effect was observed in IFN-␥-knockout mice, suggesting that the IL-18-induced reduction in the number of leukocytes was mediated by IFN-␥. IL-18 has been reported to induce TNF-␣, which has been reported to cause a reduction in the number of circulating lymphocytes 6 h after administration in rats (25,31). In this study, however, we found no induction of TNF-␣ in the serum samples of mice treated with IL-18 (data not shown), suggesting that it was unlikely that TNF-␣ was involved in IL-18-induced leukocyte reduction.…”

Section: Discussioncontrasting

confidence: 70%

Interleukin-18 Induces Acute Biphasic Reduction in the Levels of Circulating Leukocytes in Mice

Hosohara¹,

Ueda

Kashiwamura

et al. 2002

Clin Vaccine Immunol

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We investigated the acute hematological changes caused by interleukin-18 (IL-18) in mice. Intraperitoneal administration of IL-18 (2 g/mouse) resulted in biphasic decreases in the number of leukocytes in the blood. The first phase of decrease occurred within 2 h of IL-18 administration and was followed by a transient increase at 5 h. The second phase of decrease occurred at around 6 h, reaching a nadir which lasted for more than 24 h. In mice deficient in inducible nitric oxide (NO) synthase, the first phase of reduction of leukocytes did not occur although the second phase of decrease was observed. In mice deficient in gamma interferon (IFN-␥) or in mice depleted of natural killer cells and incapable of producing IFN-␥, IL-18 had no effect on the number of circulating leukocytes. Levels of nitrite and/or nitrate in the serum were elevated within 2 h after administration of IL-18, reaching a peak at 4 h and then decreasing gradually to the basal level over a 24-h period of time. On the other hand, serum IFN-␥ levels changed in a biphasic manner, reaching a peak at 2 h after IL-18 administration, followed by a decrease in the basal level and a second increase at 6 h. Levels of IL-18 receptor mRNAs also showed biphasic changes in correlation with the changes in serum IFN-␥ levels. These results suggest that the changes in the leukocyte number following IL-18 administration are mediated by NO and IFN-␥, with NO being involved in the first phase of reduction and IFN-␥ being involved in both phases.

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Section: Discussioncontrasting

confidence: 70%

Interleukin-18 Induces Acute Biphasic Reduction in the Levels of Circulating Leukocytes in Mice

Hosohara¹,

Ueda

Kashiwamura

et al. 2002

Clin Vaccine Immunol

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“…The first peak of IL-6-induced neutrophilia is therefore most likely due to demargination of peripheral neutrophils. This is consistent with the observation that the magnitude of this neutrophilia is very similar to that induced by epinephrine, a known demarginating agent in rats (77,78).…”

Section: Cytokine Effects On Leukocytessupporting

confidence: 91%

Cytokine-Induced Changes in the Leukon

Anderson

1993

Toxicol Pathol

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“…TNF-␣ activates neutrophils, causing their margination to the vascular wall and promoting a prothrombotic condition. [65][66][67][68] Similarly, prolonged hypoxia followed by reoxygenation triggers myriad biologic responses. [69][70][71][72] The PAR-1 agonist peptide that we used does not activate neutrophils or cause their margination.…”

Section: Discussionmentioning

confidence: 99%

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

Embury

Matsui²,

Ramanujam³

et al. 2004

Blood

127

121

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Microvascular occlusion in sickle cell disease can be initiated by adhesion of sickle red blood cells (RBCs) to the endothelium. Our objective in this study was to verify the relevance in vivo of our discovery that sickle RBCs adhere abnormally to endothelial P-selectin in vitro. We used computer-assisted intravital microscopy to characterize RBC flow velocity (V RBC ) in mice. We found faster V RBC of sickle RBCs in P-selectin knock-out and control mice than in sickle cell mice, which have increased endothelial cell P-selectin expression. Agonist peptide for murine protease-activated receptor-1 (PAR-1), which selectively activates mouse endothelial cells but not platelets, was used to assess the effects of endothelial cell Pselectin on microvascular flow. Suffusion of venules with this agonist stopped flow promptly in normal and sickle mice but not in P-selectin knock-out mice or in control mice pretreated with anti-P-selectin monoclonal antibody or unfractionated heparin (UFH). Agonist-induced slowing of flow was reversed rapidly by suffusion with UFH, provided flow had not already stopped. We conclude that endothelial cell P-selectin contributes to the microcirculatory abnormalities in sickle cell disease and that blocking Pselectin may be useful for preventing painful vasoocclusion in sickle cell disease. ( IntroductionMost of the morbid consequences of sickle cell disease are caused by the impairment of blood flow in the microvasculature. 1 Traditional understandings attribute the microvascular occlusion to an increase in blood viscosity caused by intraerythrocytic polymerization of deoxygenated sickle hemoglobin and the consequent sickling and rigidification of red blood cells (RBCs). 2 Kinetic considerations predict that, in the absence of preexisting intraerythrocytic polymer, impairment of blood viscosity will occur after the RBC has entered into veins too large to be occluded by rigid sickled RBCs 3 and that polymerization will occur within vessels small enough to be occluded by individual sickled RBCs only when their transit through the microcirculation is delayed.Among the factors that can prolong the transit time of sickle RBCs through the microvasculature are several polymerizationindependent processes, including vascular constriction, coagulation, inflammation, and cellular adhesion. 4 Experimental evidence supports a 2-step mechanism of vasoocclusion initiated by the binding of an adhesive subset of sickle RBCs to the vascular endothelium and completed by the logjamming of more rigid sickle RBCs behind the adherent nidus. 5 This discovery has provided an understanding of the onset of painful vasoocclusion that is lacking from detailed explications of hemoglobin S polymerization and RBC sickling and notions of systemic deoxygenation 6 and inspired a profusion of research into mechanisms of adhesion and adhesion-blocking therapies. 7,8 The expression of cytoadhesion molecules on endothelial cells isolated from the circulating blood of patients with sickle cell disease 9 and on intact endothelial c...

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Mechanisms of Tumor Necrosis Factor Alpha-Induced Lymphopenia, Neutropenia, and Biphasic Neutrophilia: A Study of Lymphocyte Recirculation and Hematologic Interactions of TNFα With Endogenous Mediators of Leukocyte Trafficking

Cited by 57 publications

References 0 publications

Interleukin-18 Induces Acute Biphasic Reduction in the Levels of Circulating Leukocytes in Mice

Interleukin-18 Induces Acute Biphasic Reduction in the Levels of Circulating Leukocytes in Mice

Cytokine-Induced Changes in the Leukon

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

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