Binding of iron beads to sialic acid residues on macrophage membranes stimulates arachidonic acid metabolism.
Phagocytosis of carbonyl iron beads by rat alveolar macrophages induces the production of cyclooxygenase and lipoxygenase metabolites of arachidonic acid (AA). To study the relationship between the phagocytic event and AA metabolite production, rat alveolar macrophages were pretreated with cytochalasin D, which suppresses particle internalization, but not binding to the plasma membrane. The cells were then challenged with iron particles. Binding of the particles, without internalization, was a stimulus sufficient to initiate the AA metabolic cascade; this was true for cyclo- as well as for lipoxygenase pathways. To characterize the receptor responsible for iron bead binding to membranes, macrophages were pretreated with the lectin, wheat germ agglutinin. This treatment suppressed iron bead binding, phagocytosis, and the production of AA metabolites. Succinylated wheat germ agglutinin, which binds only to N-acetylglucosamine, prevented none of these events. Wheat germ agglutinin alone had a stimulatory activity on AA metabolism which was biphasic in nature, i.e., production of cyclooxygenase metabolites first and then leukotriene B4 upon rechallenge. Succinylated wheat germ agglutinin was devoid of such an effect on AA metabolism. Thus, AA metabolite production by alveolar macrophages during phagocytosis seems to be stimulated by initial binding of particles to the plasma membrane. Membrane-bound sialic acid residues appear to be instrumental in binding of carbonyl iron beads with consequent initiation of the AA metabolic cascade.
D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D007501:Iron / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D012794:Sialic Acids / Q000378:metabolism*; D014909:Wheat Germ Agglutinins
D001095:Arachidonic Acids; D037102:Lectins; D008823:Micelles; D012794:Sialic Acids; D014909:Wheat Germ Agglutinins; D016718:Arachidonic Acid; D007501:Iron; D000117:Acetylglucosamine