Cytoplasmic calcium fluxes induced in cytotoxic effector cells by engagement of Fc gamma receptors I, II, and III.
Changes in the intracellular calcium ion concentration ([Ca2+]i) of monocytes, granulocytes, and NK cells have been studied following either (1) independent cross-linking of Fc gamma receptors (Fc gamma R) I, II, or III, with F(ab gamma')2 fragments of monoclonal antibodies; or (2) linking of a selected Fc gamma R to a tumour cell target with bispecific F(ab' gamma)2 antibodies. Upon cross-linking each Fc gamma R with antibody an increase in the [Ca2+]i was observed, although all receptors apart from Fc gamma RIII on NK cells required additional cross-linking with an anti-mouse Fab' gamma. These results indicate that each type of receptor can transduce signals to the cell independently. Bispecific antibodies (anti-Fc gamma R x anti-target) linking cytotoxic Fc gamma R-bearing effector cells to tumour target cells also mediated increases in [Ca2+]i for all Fc gamma R tested except for Fc gamma RIII on granulocytes. The failure to transduce a signal via this receptor may be related to the GPI link, which is in contrast to the transmembrane link of Fc gamma RIII on NK cells. Significant lysis of tumour cell targets occurred when bispecific antibodies recruited NK cells or monocytes, but not granulocytes, via Fc gamma R. Chelation of intracellular Ca2+ in the effector cells reduced the observed lysis, suggesting a role for Ca2+ in the pathways leading to cytotoxicity.
Curnow
S J
SJ
Lymphoma Research Unit, Tenovus Laboratory, General Hospital, Southampton, UK.
Glennie
M J
MJ
Stevenson
G T
GT
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D011961:Receptors, Fc; D017452:Receptors, IgG; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium