Stimulation of human polymorphonuclear leukocytes by leukotriene B4 and platelet-activating factor: an ultrastructural and pharmacological study
| Autor: | A. G. Rossi, C. J. P. Jones, D. E. Macintyre, R. M. Mcmillan |
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| Rok vydání: | 1993 |
| Předmět: |
Adult
Leukotriene B4 Neutrophils Immunology Biology Pharmacology In Vitro Techniques chemistry.chemical_compound Acetylglucosaminidase Immunology and Allergy Humans Cytochalasin Lipoxygenase Inhibitors Platelet Activating Factor Cytochalasin B Cell Aggregation Platelet-activating factor Dose-Response Relationship Drug Ionomycin Degranulation hemic and immune systems Cell Biology respiratory system N-Formylmethionine leucyl-phenylalanine Cell aggregation N-Formylmethionine Leucyl-Phenylalanine Microscopy Electron chemistry Biochemistry Quinolines lipids (amino acids peptides and proteins) Muramidase |
| Zdroj: | Journal of leukocyte biology. 53(2) |
| ISSN: | 0741-5400 |
| Popis: | Human polymorphonuclear leukocytes (PMNs) stimulated by N-formylmethionyl-leucyl- phenylalanine (fMLP), leukotriene B4 (LTB4) and platelet-activating factor (PAF) showed a similar sequence of ultrastructural changes. Exposure of unstirred PMNs to diese soluble stimuli induced a rapid (within 10 s) plasma membrane ruffling followed by polarization of cells associated with formation of broad agranular lamel, lipodia (maximal by 30 s). Similar changes were observed in stirred PMN suspensions except that the polarized cells formed multicellular aggregates with the agranular lamellipodia extending outward from the clumps. In addition, these receptor-directed agonists induced concentration-dependent PMN aggregation that was rapid and reversible, and in cells pretreated with cytochalasin B the agonists induced a degranulatory response. The calcium ionophore ionomycin also activated PMNs but, in contrast to the other stimuli, ionomycin produced irreversible aggregation and evoked enzyme release in the absence of cytochalasin B. Ionomycin stimulated LTB4 release, whereas the response induced by PAF or fMLP was barely detectable. The possible role of LTB4 and PAF in mediating responses to other agonists was investigated pharmacologically using the 5-lipoxygenase inhibitor PF 5901 and a specific PAF antagonist, kad- surenone. PF 5901 blocked ionomycm-induced LTB4 release but did not inhibit aggregation or degranulation induced by ionomycin, PAF, fMLP, or LTB4. Kad- surenone blocked PAF-induced aggregation and degranulation but not responses to LTB4, ionomycin, or fMLP. We conclude that LTB4 and PAF are potent activators of human PMNs that act independently of one another and that these lipids appear not to be involved in the responses to the other agonists studied. J. Leukoc. Biol. 53: 117–125; 1993. |
| Databáze: | OpenAIRE |
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