Blockade of PAF receptors controls interleukin-8 production by regulating the activation of neutrophil CD11/CD18

• Published in: European journal of pharmacology Vol. 425; no. 1; pp. 65 - 71
• Main Authors: Au, Bo-ting, Teixeira, Mauro M, Collins, Paul D, Williams, Timothy J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 03.08.2001; Elsevier
• Subjects: Biological and medical sciences; CD11 Antigens - metabolism; CD11/CD18 activation; CD18 Antigens - metabolism; Cells, Cultured; Cytochalasins - pharmacology; Dihydropyridines - pharmacology; Epitopes - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Imidazoles - pharmacology; Immunobiology; Inflammation; Interleukin-8; Interleukin-8 - biosynthesis; Molecular and cellular biology; Myeloid cells: ontogeny, maturation, markers, receptors; Neutrophil; Neutrophil Activation - drug effects; Neutrophils - drug effects; Neutrophils - metabolism; PAF (platelet activating factor); Phagocytosis; Phagocytosis - drug effects; Platelet Membrane Glycoproteins - antagonists & inhibitors; Polynuclears; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Time Factors; Zymosan; Zymosan - pharmacokinetics; Zymosan; Neutrophil; CD11/CD18 activation; PAF (platelet activating factor); Interleukin-8; Phagocytosis; Human; Interleukin; Cytokine; Cellular immunity; Inflammation; In vitro; Biological activity; Platelet activating factor; Regulation(control); Antagonist; Mechanism of action; Interleukin 8; Biological receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)01141-4

The production of interleukin-8 by neutrophils in response to particulate stimuli may play a role in the recruitment and activation of further neutrophils in an inflammatory reaction. Here, we have evaluated the sequence of early events leading to interleukin-8 production by phagocytosing neutrophils. Kinetic experiments showed that the phagocytosis of zymosan particles by human neutrophils was rapid in onset. In contrast, interleukin-8 production was more protracted and only detectable 6 h later. Nevertheless, inhibition of phagocytosis with cytochalasins B or D suppressed the late interleukin-8 production. Activation of neutrophils with zymosan failed to enhance CD11/CD18 expression on the neutrophil surface but led to an increase in the expression of an activation-dependent epitope on CD11/CD18. Pretreatment with the platelet-activating factor (PAF) receptor antagonist, UK-74505 (4-(2-chlorophenyl)-1,4-dihydro-3-ethoxycarbonyl-6-methyl-2-[4-(2-methylimidazol[4,5- c]pyrid-1-yl)phenyl]-5-[ N-(2-pyridyl)carbamoyl]pyridine), significantly blocked the increase in the expression of the activation epitope, resulting in inhibition of the phagocytosis of zymosan and interleukin-8 production. In conclusion, the activation of neutrophils with zymosan leads to the activation of PAF receptors and this is followed by activation of CD11/CD18, phagocytosis of zymosan particles and subsequent interleukin-8 release.