Inhibition of chemotactic migration of human neutrophilic granulocytes by recombinant human granulocyte-macrophage colony-stimulating factor

doi:10.1016/0162-3109(90)90049-K

Immunopharmacology

Volume 19, Issue 2, March–April 1990, Pages 139-143

Immunopharmacology

https://doi.org/10.1016/0162-3109(90)90049-K Get rights and content

Abstract

Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was analysed for effects on the migration of human neutrophilic granulocyte by the Boyden chamber assay. At concentrations ranging from 0.1 to 10 000 U/ml (or 10⁻¹² to 10⁻⁷ mol/1) GM-CSF had neither chemokinetic nor chemotactic activity. When added to the cells in the upper compartment of the chamber GM-CSF dose-dependently inhibited the chemotactic migration towards the tripeptide f-Met-Leu-Phe and the complement split product C5a. Chemotaxis towards f-Met-Leu-Phe was inhibited more efficiently by GM-CSF than C5a-induced migration.

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Cited by (24)

Neutrophil priming by cytokines and vitamin D binding protein (Gc- globulin): Impact on C5a-mediated chemotaxis, degranulation and respiratory burst
1999, Molecular Immunology
At the site of acute inflammation, leukocytes are confronted with multiple mediators which are expected to modulate each other with respect to cell responses to the individual ligand. Previous contact of neutrophils with pro-inflammatory cytokines, such as TNF-α or GM-CSF, or with the vitamin D binding protein (Gc-globulin) leads to the alteration of either multiple or rather distinct C5a-mediated neutrophil functions. Gc-globulin, the transport protein for 25-(OH)-D₃, serves selectively as a cochemotactic factor for C5a/C5a_desArg. In contrast, TNF-α and GM-CSF, previously shown to modulate FMLP-induced neutrophil responses, are able to reduce C5a-mediated neutrophil chemotaxis, but augment their degranulation and respiratory burst activity. Cytokine priming was shown to be accompanied by a down-regulation of C5a receptors (CD88) whereas vitamin D binding protein had no impact on the level of neutrophil C5a receptors. C5a itself diminishes chemotaxis as well as degranulation and oxidative burst in response to a second dose of the same ligand (homologous desensitization). A similar effect, termed heterologous desensitization, occurs, if cell responses to a given mediator (e.g. to C5a) are reduced or even abolished upon the activation of another receptor of the same G-protein coupled chemoattractant receptor subfamily (e.g. receptors for FMLP or IL-8). In concert with C5a, certain molecules may either augment chemotaxis or shift neutrophil effector functions from migration to exocytosis, an essential step within the sequence of events in a coordinated inflammatory response.
Increase in granulocyte-macrophage-colony-stimulating factor secretion and the respiratory burst with decreased L-selectin expression in hyper-IgE syndrome patients
1999, Annals of Allergy, Asthma and Immunology
The hyper-IgE syndrome is a primary immunodeficiency characterized by severe recurrent abscesses, pneumonia with pneumatocele formation, and elevated serum IgE. Eosinophilia, neutrophil chemotactic defects, and marked tissue damage are frequently present in this syndrome.
To study whether functional changes in cytokines, adhesion molecules, and neutrophils might help explain these clinical observations.
The following functions were analyzed in patients with the hyper-IgE syndrome and in controls: (1) production of granulocyte-macrophage-colony-stimulating factor by peripheral blood mononuclear cells by ELISA; (2) respiratory burst and reactive oxygen intermediates production by peripheral neutrophils using the luminol-enhanced chemiluminescense technique; and (3) expression of l-selectin on granulocytes and lymphocytes by flow cytometry.
Patients with hyper-IgE syndrome had significantly increased production of granulocyte-macrophage-colony-stimulating factor by resting or stimulated mononuclear cells, increased generation of reactive oxygen intermediates by neutrophils treated with opsonized zymosan, and reduced l-selectin expression on quiescent and activated granulocytes and lymphocytes.
Our results suggest that an important feature of the hyper-IgE syndrome is the increased production of granulocyte-macrophage-colony-stimulating factor, which may explain the reduced l-selectin expression, decreased chemotaxis, and increased oxygen radical production and tissue damage in this disease.
The role of cyclic nucleotides in neutrophil migration
1996, General Pharmacology
- 1.
  1. The literature concerning the effects of cAMP and especially cGMP on neutrophil migration is reviewed.
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  3. Some physiologically active peptides such as granulocyte-macrophage colony-stimulating factor (GM-CSF), atrial natriuretic factor, and endothelin appear to modify neutrophil migration via a cGMP-dependent mechanism.
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  4. Dependent on concentration and conditions (random migration vs. fMLP-activated migration, using nitric oxide (NO), NO donors, and inhibitors of NO synthase), NO has stimulatory or inhibitory effects on neutrophil migration.
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  5. The differential effects of cGMP and cAMP on neutrophil migration are discussed with regard to intracellular actions, metabolism, interaction with calcium, and relation to structural changes required for cell movement.
The effect of GM-CSF and G-CSF on human neutrophil function
1995, Immunopharmacology
A direct comparison of GM-CSF and G-CSF in a panel of in vitro neutrophil-function assays was performed to investigate any differences in activity profiles. In our modified chemotactic assay, GM-CSF rapidly increased the migratory capacity of polymorphonuclear cells (PMNs) to move toward fMLP and LTB₄. In contrast, G-CSF only stimulated PMN migration towards fMLP. GM-CSF, but not G-CSF, increased PMN cytotoxic killing of C. albicans blastospores. The expression of PMN surface antigens associated with Fc- and complement-mediated cell-binding (FcγR1, CR-1 and CR-3), and adhesion signalling (ICAM-1), was increased after the exposure of GM-CSF, but not to G-CSF. In contrast these CSFs demonstrated relative equipotency in their ability to induce PMN anti-bacterial phagocytosis, and to restore the Staphylococcus aureus killing capacity of dexamethasone-suppressed neutrophils. The phagocytic activity of PMNs for opsonized yeast, as well as hexose-monophosphate shunt activity, was equivalent following GM-CSF or G-CSF treatment. We discuss the significance of the difference in activity profiles in this article.)
Mechanisms and mediators of neutrophilic leukocytosis
1994, Immunopharmacology
Homeostatic mechanisms controlling levels of circulating leukocytes have been an enigma in the field of hematology for decades. The short circulating half-life of PMNs relative to other leukocytic cell types, and their critical role as a front line of defense against infectious agents ascribes particular importance to this regulatory process. While strident advances have expanded our knowledge of how leukocytes develop and mature in the bone marrow, their regulation and mechanisms for transport into the circulation remain largely unexplained. The relatively recent availability of recombinant cytokines and other highly purified biologic mediators, as well as the development of monoclonal antibodies against specific leukocyte adhesion molecules have led to new insights and renewed interest in this dynamic process (Springer, 1990; Petrides and Dittmann, 1990). This article reviews recent advances in defining the cellular and molecular interactions involved in leukocyte recruitment by various mediators, and proposes conceptual models for regulation of circulating leukocyte levels.
The effect of cyclic GMP and cyclic AMP on migration by electroporated human neutrophils
1993, European Journal of Pharmacology: Molecular Pharmacology
Human neutrophils retain the ability to migrate when they are electroporated; this enables the study of potential mediators by direct application to the cell interior. Cyclic GMP strongly enhances random migration by electroporated human neutrophils. The effect is maximal at a concentration of 10 μM. The potentiating effect of cGMP is chemokinetic. Chemotaxis of electroporated neutrophils activated by formylmethionylleucylphenylalanine (fMLP) is stimulated by cGMP at concentrations up to 10 μM; higher concentrations inhibit chemotaxis. Cyclic AMP resembles cGMP in that both activation and inhibition may occur. However, activation occurs over a very small concentration range, and inhibition is a predominant feature. Cyclic nucleotide-activated migration is dependent on Ca²⁺, in contrast with activation of migration by fMLP.

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Inhibition of chemotactic migration of human neutrophilic granulocytes by recombinant human granulocyte-macrophage colony-stimulating factor

Abstract

Blood

Blood

J Invest Dermatol

Biochem Biophys Res Commun

Immunobiology

Blood

Human recombinant granulocyte-macrophage colony-stimulating factor increases cell-to-cell adhesion and surface expression of adhesion-promoting surface glycoproteins on mature granulocytes

J Clin Invest

Recombinant human granulocyte-macrophage colony-stimulating factor (rH GM-CSF) regulates f Met-Leu-Phe receptors on human neutrophils

Immunology

The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leukocytes

J Exp Med

Temporal adaptation of neutrophil oxidative responsiveness to n-formyl-methionyl-leucyl-phenylalanine. Acceleration by granulocyte-macrophage colony-stimulating factor

J Immunol

Purified human granulocyte-macrophage colony-stimulating factor: direct action on neutrophils

Science