Lipopolysaccharide and cytokine augmentation of human monocyte IgA receptor expression and function.
Receptors for IgA (Fc alpha R) are found on phagocytic cells in the peripheral blood and tissues associated with mucosal areas where IgA Abs constitute a major line of defense. Because Fc alpha R are capable of triggering protective functions of monocytes and neutrophils, such as phagocytosis and the oxidative burst, they may be important in amplifying the antimicrobial effects of IgA. Various cytokines play a role in regulating function and FcR expression of monocytes, macrophages, and neutrophils. The present studies examine the modulation of monocyte Fc alpha R by LPS and cytokines. LPS strongly up-regulated monocyte Fc alpha R expression. TNF and IL-1, produced in response to LPS, promoted Fc alpha R increase, as did GM-CSF; whereas IFN-gamma down-regulated Fc alpha R. Increased receptor expression was accompanied by augmented IgA-mediated phagocytosis. An increase in Fc alpha R-specific mRNA was detected in monocytes treated with TNF, IL-1, GM-CSF, and LPS; whereas message was reduced in cells treated with IFN-gamma. Monocyte-derived macrophages and cells of the Monomac 6 monocyte-like line expressed greater numbers of Fc alpha R than monocytes but were less responsive to LPS and TNF. Cell lines THP-1 and U937, which expressed similar or lower levels of Fc alpha R than monocytes, displayed an increase in Fc alpha R in response to LPS and, to various degrees, to TNF, IL-1, and GM-CSF. These results indicate that Fc alpha R on monocytes are modulated by endotoxin and an array of cytokines distinct from those that regulate expression of FcR for IgG.
Shen
L
L
Dartmouth Medical School, Lebanon, NH 03756.
Collins
J E
JE
Schoenborn
M A
MA
Maliszewski
C R
CR
D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; C045281:IgA receptor; D008070:Lipopolysaccharides; D011961:Receptors, Fc