Polarized distribution of Na+,K+-ATPase in giant cells elicited in vivo and in vitro.
Giant cell formation was analyzed to determine whether it results in the high level of Na+,K+-ATPase expression that characterizes multinucleated cells such as osteoclasts. Giant cells and fusing alveolar macrophages were subjected to morphological, immunological, and biochemical studies. Both subunits of the Na+,K+-ATPase were found to be present on the plasma membrane of giant cells. Their localization was restricted to the non-adherent domain of the cell surface. Dynamic studies of giant cell differentiation demonstrated that on culture and/or multinucleation, an increase in sodium pump alpha-subunit synthesis occurred and led to a high level of expression of Na pumps. Conversely, the adherent plasma membrane of giant cells was enriched in a lysosomal membrane antigen. This study demonstrates that culture and/or multinucleation induces a significant increase in the expression of sodium pumps. The polarized distribution of these pumps and of a lysosomal component suggests that fusing macrophages undergo biochemical and morphological alterations which prepare them for a new and specialized function in chronic inflammatory reactions. Giant cells may offer a suitable model system to study the differentiation of other related multinucleated cells, such as osteoclasts.
Vignery
A
A
Department of Orthopaedics, Yale University School of Medicine, New Haven, Connecticut 06511.
Niven-Fairchild
T
T
Ingbar
D H
DH
Caplan
M
M
D000818:Animals; D002459:Cell Fusion; D002645:Chickens; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005549:Foreign-Body Reaction / Q000201:enzymology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008247:Lysosomes / Q000032:analysis; D008264:Macrophages / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D011233:Precipitin Tests; D011506:Proteins / Q000032:analysis; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis* / Q000096:biosynthesis
D011506:Proteins; C018589:lysosomal proteins; D004247:DNA; D000254:Sodium-Potassium-Exchanging ATPase