Modulation of human neutrophilic granulocyte functions by recombinant human tumor necrosis factor and recombinant human lymphotoxin. Promotion of adherence, inhibition of chemotactic migration and superoxide anion release from adherent cells.
Recombinant human tumor necrosis factor (TNF) and recombinant human lymphotoxin (LT) were analyzed for their effects on inflammation-related functions of human polymorphonuclear neutrophilic granulocytes (PMN) in vitro, TNF at a concentration of 10 U/ml (corresponding to 10(-11) mol/l) enhanced PMN adherence to nylon fibres. It strongly inhibited the chemotactic migration of PMN in the Boyden chamber assay towards the chemotactic tripeptide formyl-methionyl-leucyl-phenylalanine (FMLP), C5a, LTB4 and a monocyte-derived chemotaxin (MOC) without affecting random migration and without being chemotactic itself. It did not stimulate superoxide anion (-O2.) production of PMN in suspension. However, it induced considerable -O2. release from PMN that had become adherent on nylon fibres. All these effects were abrogated by prior incubation of the cytokine with polyclonal and monoclonal antibodies against TNF. LT concentrations of 1,000 U/ml or higher were required to observe a moderate inhibition of chemotactic migration towards the above chemotactic factors and to elicit some -O2. production from nylon fibre-adherent PMN. LT did not increase the adherence of PMN to nylon fibres and it was not chemotactic. The results indicate that TNF is a potent modulator of PMN functions.
Kownatzki
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E
Abteilung Experimentelle Dermatologie, Universitäts-Hautklinik, Freiburg.
Kapp
A
A
Uhrich
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S
D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides