Modulation of human neutrophil and monocyte chemotaxis and superoxide responses by recombinant TNF-alpha and GM-CSF.
The effects of recombinant TNF and GM-CSF on human peripheral blood neutrophil and monocyte chemotaxis and the superoxide response were studied. TNF exhibited a slight chemotactic activity for both cell types. Preincubation of neutrophils with as little as 40 units/ml strongly inhibited the neutrophil chemotaxis towards f-Met-Leu-Phe. The inhibition of monocyte chemotaxis required higher concentrations of TNF (greater than 400 units/ml). TNF at concentrations higher than 500 units/ml enhanced the generation of superoxide anions by neutrophils stimulated with f-Met-Leu-Phe. In contrast, TNF even at 2,000 units/ml did not prime monocytes for enhanced superoxide response. GM-CSF alone did not exhibit any chemotactic activity for any of the cell types tested. Preincubation of cells with GM-CSF inhibited chemotaxis of neutrophils but not of monocytes. GM-CSF was as potent as TNF in enhancing the generation of superoxide response by neutrophils. However, GM-CSF did not have any effect on monocyte superoxide response. The priming ability of TNF and GM-CSF on neutrophils was heat-sensitive. We conclude that TNF and GM-CSF play a more pronounced regulatory role on neutrophils than on monocytes. Inhibition of neutrophil chemotaxis followed by enhancement of the superoxide response by TNF and GM-CSF may provide an attractive mechanism by which these cytokines assist in fighting invading microorganisms.
Kharazmi
A
A
State Serum Institute, Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Nielsen
H
H
Bendtzen
K
K
D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor