Fc gamma RIIa, not Fc gamma RIIb, is constitutively and functionally expressed on skin-derived human mast cells.
The expression of FcgammaR by human skin-derived mast cells of the MC(TC) type was determined in the current study. Expression of mRNA was analyzed with microarray gene chips and RT-PCR; protein by Western blotting and flow cytometry; function by release of beta-hexosaminidase, PGD(2), leukotriene C(4) (LTC(4)), IL-5, IL-6, IL-13, GM-CSF, and TNF-alpha. FcgammaRIIa was consistently detected along with FcepsilonRI at the mRNA and protein levels; FcgammaRIIc was sometimes detected only by RT-PCR; but FcgammaRIIb, FcgammaRI, and FcgammaRIII mRNA and protein were not detected. FcgammaRIIa-specific mAb caused skin MC(TC) cells to degranulate and secrete PGD(2), LTC(4), GM-CSF, IL-5, IL-6, IL-13, and TNF-alpha in a dose-dependent fashion. FcepsilonRI-specific mAb caused similar amounts of each mediator to be released with the exception of LTC(4), which was not released by this agonist. Simultaneous but independent cross-linking of FcepsilonRI and FcgammaRIIa did not substantially alter mediator release above or below levels observed with each agent alone. Skin MC(TC) cells sensitized with dust-mite-specific IgE and IgG, when coaggregated by Der p2, exhibited enhanced degranulation compared with sensitization with either IgE or IgG alone. These results extend the known capabilities of human skin mast cells to respond to IgG as well as IgE-mediated signals.
Zhao
Wei
W
Department of Pediatrics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Kepley
Christopher L
CL
Morel
Penelope A
PA
Okumoto
Lawrence M
LM
Fukuoka
Yoshihiro
Y
Schwartz
Lawrence B
LB
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000502:physiology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D007074:Immunoglobulin G / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D012333:RNA, Messenger / Q000096:biosynthesis; D011940:Receptor Aggregation / Q000276:immunology; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D003432:Cross-Linking Reagents; C080568:Fc gamma receptor IIA; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D009596:Nitrophenols; D010648:Phenylacetates; D012333:RNA, Messenger; D017452:Receptors, IgG; C026242:4-hydroxy-5-nitrophenyl acetic acid; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E