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Abstract
Little IS known about the influence of IL-2 on phagocytes. We now describe the effects of human recombinant IL-2 on human neutrophil and monocyte functions related to mobility, phagocytosis, glucose uptake, respiration and degranulation. Neutrophil adherence and hexose monophosphate shunt activities were both suppressed after incubation with IL-2. IL-2 had no effect on neutrophil migration, phagocytosis, deoxyglucose uptake or degranulation, ionocytes demonstrated a greater sensitivity to IL-2 with suppression of monocyte adherence, random and stimulated migration, glucose uptake and hexose monophosphate shunt activity, even after addition of phorbol myristate acetate. Monocyte phagocytosis and degranulation were not affected. All of the effects observed were dose-dependent within a biologically active range for IL-2. These studies suggest that IL-2 may have an important down-regulatory role across a broad range of monocyte functions including movement, deoxyglucose uptake and respiration. However, its role in regulation of neutrophil function is limited to adherence and respiration. IL-2 may be a more versatile cytokine than has previously been appreciated.
Highlights
Interleukin-2 (IL-2) is a glycoprotein cytokine with a broad range of immunoregulatory functions
It has been shown to play a role in the differentiation and proliferation of both B- and T-lymphocytes by up- or down-regulation of various subsets; 1-4 it can directly augment the cytotoxic activity of natural killer cells and large granular lymphocytes,[5,6,7] but may indirectly suppress this function, IL-2 has been implicated in monocyte/macrophage regulation as these cells have been shown to bind IL-2 via specific membrane receptors[9,10,11] and it has been shown to enhance monocyte cytotoxic activity[2] and induce macrophage resistance to infection
Neutrophils have only recently been recognized as target cells for immunoregulatory cytokines. 7’8 In the light of evidence that IL-2 modulates the activities of various cell types via pathways other than the Tac protein receptor,3’15’6 we set out to compare the effect of IL-2 on two immunocyte subsets classically devoid of Tac protein expression: the human peripheral blood mononuclear phagocytes and polymorphonuclear phagocytes
Summary
Interleukin-2 (IL-2) is a glycoprotein cytokine with a broad range of immunoregulatory functions. 13 The most widely studied of the membrane receptors through which the IL-2 molecule mediates its effects is the Tac protein, which is expressed on primed or preactivated cells. 13 There are, a number of other cell membrane proteins on the surfaces of resting and stimulated cells, which bind or are phosphorylated by IL-2. 4-6 While resting monocytes are devoid of the Tac receptor protein, expression has been shown to occur following culture with a number of classical stimuli including lipopolysaccharide and interferon-. 7’8 In the light of evidence that IL-2 modulates the activities of various cell types via pathways other than the Tac protein receptor,3’15’6 we set out to compare the effect of IL-2 on two immunocyte subsets classically devoid of Tac protein expression: the human peripheral blood mononuclear phagocytes (monocytes) and polymorphonuclear phagocytes (neutrophils) Neutrophils have only recently been recognized as target cells for immunoregulatory cytokines. 7’8 In the light of evidence that IL-2 modulates the activities of various cell types via pathways other than the Tac protein receptor,3’15’6 we set out to compare the effect of IL-2 on two immunocyte subsets classically devoid of Tac protein expression: the human peripheral blood mononuclear phagocytes (monocytes) and polymorphonuclear phagocytes (neutrophils)
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