Human neutrophils are selectively activated by independent ligation of the subunits of the CD11b/CD18 integrin.
The yeast cell wall preparation zymosan is a particulate stimulus for human neutrophils (PMNs). Unopsonised zymosan particles bind to the PMN CD11b/CD18 integrin and are phagocytosed, leading to activation of the 5-lipoxygenase pathway and release of the lipid chemotaxin leukotriene B4 (LTB4). Specific monoclonal antibodies (mAbs) to CD11b and to CD18 were used in the present study to evaluate the contribution of each chain to these processes. All four anti-CD18 mAbs but none of five anti-CD11b mAbs dose-dependently blocked PMN phagocytosis of zymosan. Nevertheless, all anti-CD11b mAbs and all anti-CD18 mAbs significantly inhibited zymosan-stimulated LTB4 release in a dose-dependent manner. In addition, there was a dose-dependent stimulation of LTB4 release resulting from the specific ligation and cross-linking of either chain of the integrin heterodimer. Thus zymosan-stimulated LTB4 release is initiated by signals from both chains of the CD11b/CD18 integrin, whereas only CD18 is essential for phagocytosis.
Petersen
M M
MM
Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, United Kingdom.
Steadman
R
R
Williams
J D
JD
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D018604:Epitope Mapping; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000378:metabolism; D046911:Macromolecular Substances; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000502:physiology*; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D010587:Phagocytosis; D011961:Receptors, Fc / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D015054:Zymosan / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D000939:Epitopes; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D007975:Leukotriene B4; D015054:Zymosan