Human pulmonary macrophage-derived mucus secretagogue.
Human pulmonary macrophages (PM) obtained from surgically removed human lung tissue released a factor after exposure to activated zymosan that caused cultured human airways to release increased amounts of radiolabeled mucous glycoproteins. The factor was released maximally after 4-8 h of zymosan exposure and caused a dose-related increase in glycoprotein release; it was termed macrophage-derived mucus secretagogue (MMS). MMS release was produced in a dose-dependent fashion by activated but not by nonactivated zymosan. The activation of zymosan was C3 dependent, and C3b-coated Sepharose was also an effective stimulant. The data suggested that cell surface activation of the PM was a sufficient stimulus to cause MMS release and that both C3-dependent activation as well as Fc receptor activation were effective. The synthesis of MMS was sensitive to cycloheximide, and no active MMS was detectable intracellularly. To determine if MMS might be one of the oxidative derivatives of arachidonic acid, PM were incubated with cyclooxygenase and lipoxygenase inhibitors before activation. These maneuvers did not influence MMS generation. MMS-rich supernatants were then extracted into organic solvents or exposed to lipophilic resin; in both cases, MMS remained in the aqueous phase. Thus, MMS is not a derivative of arachidonic acid. Sequential fractionation of MMS on ultramembrane and gel filtration followed by isoelectric focusing and gel filtration indicated that MMS is a small (approximately 2000 daltons), acidic (pI, 5.15) molecule. Therefore, surface activation of human PM results in the synthesis and release of a small acidic molecule that causes airway mucous glands to secrete increased quantities of mucous glycoproteins.
D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015846:Monokines; D009093:Mucus / Q000032:analysis / Q000378:metabolism*; D009895:Opsonin Proteins / Q000502:physiology; D010587:Phagocytosis; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000302:isolation & purification; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D015054:Zymosan / Q000494:pharmacology
D006023:Glycoproteins; D015846:Monokines; D009895:Opsonin Proteins; D011448:Prostaglandin Antagonists; D011506:Proteins; D015054:Zymosan