Modulation and induction of eosinophil chemotaxis by granulocyte- macrophage colony-stimulating factor and interleukin-3

Abstract

Eosinophilia and eosinophil function are regulated by cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin- 3 (IL-3), and IL-5. We have investigated the modulatory role of GM-CSF and IL-3 on the platelet-activating factor (PAF)-, neutrophil- activating factor (NAF/IL-8)-, leukotriene B4 (LTB4)-, N-formyl- methionyl-leucyl-phenylalanine (FMLP)-, and human complement factor C5a- induced chemotaxis of eosinophils from normal individuals. These eosinophils show a chemotactic response toward PAF, LTB4, and C5a, but not to NAF/IL-8 and FMLP. Preincubation of the eosinophils with picomolar concentrations of GM-CSF caused a significant increase in the response toward LTB4 and induced a significant chemotactic response toward NAF/IL-8 and FMLP. Preincubation of the eosinophils with picomolar concentrations of IL-3 also induced a chemotactic response toward NAF/IL-8 and FMLP, and enhanced the PAF-induced chemotaxis response toward C5a was not influenced by both cytokines. Nanomolar concentrations of GM-CSF or IL-3 caused a significant inhibition of the C5a-induced chemotaxis. The LTB4-induced chemotaxis was also significantly inhibited in case of GM-CSF. At these concentrations both GM-CSF and IL-3 acted as chemotaxins for eosinophils were washed after pretreatment with GM-CSF and IL-3 the potentiation of the chemotactic response remained, whereas the inhibitory mode of action disappeared. Our data indicate that at picomolar concentrations the cytokines GM-CSF and IL-3 can modulate eosinophil chemotaxis and at nanomolar concentrations these cytokines can act as chemotaxins for eosinophils.

Asthma, Viruses, and Nitric Oxide

“…The idea that cells such as eosinophils can be 'primed' in vivo by exposure to circulating cytokines such as interleukin-5 (IL-5), interleukin-3 (IL-3), or GM-CSF, in asthmatics, but not normals, has been suggested as a plausible explanation for the differential recruitment. Studies have shown that eosinophils from patients with asthma have increased chemotactic and chemokinetic responses compared to eosinophils from nonasthmatic subjects, suggesting that eosinophils from asthmatics are primed to respond to chemotactic stimuli (104)(105)(106). In vitro studies have demonstrated that cytokines such as IL-5 and GM-CSF activate eosinophils by enhancing adhesion molecule expression and increasing transendothelial and transepithelial migration (107)(108)(109).…”

The physiology of murine germinal center reactions

“…For example, local TNF-a and IL-1 p production induces secretion of inflammatory mediators .such as IL-6, IL-8 and Rantes, facilitating extravasation of eoslnophils and lymphocytes (60,61). IL-3 and IL-5 prime while GM-CSF attract eosinophils into the lung parenchyma and airways and serve to activate other cell types (62)(63)(64). The allergen-specific immunoglobulin, IgE, also influences the activation of many populations including mast cells, monocytes, macrophages, eosinophils.…”

Constitutive and Inducible Cytokine mRNA Expression in the Human Mast Cell Line HMC‐1

“…Both IL-3 and GM-CSF were first described as colony-stimulating factors, inducing colony-formation of bone marrow cells. In addition to their role in haematopoiesis, IL-3 and GM-CSF can influence inflammation by recruiting, priming and activating inflammatory cells such as basophils and eosinophils [20][21][22][23]. Thus, by combining expression of pro-inflammatory cytokines and chemokines [8] and other cytokines attracting leucocytes, such as IL-3 and GM-CSF, mast-cell derived cytokines can act in sequence.…”