alpha2-macroglobulin modulates the immunoregulatory function of the lipocalin placental protein 14.
Human placental protein 14 (PP14; also known as glycodelin and progesterone-associated endometrial protein) is an immunosuppressive protein of the lipocalin structural superfamily. Mechanisms regulating serum PP14's immunosuppressive activity remain to be elucidated. In the present study, an interaction between PP14 and a major serum protein carrier, alpha(2)-macroglobulin (alpha(2)M), was documented for the first time. Using native gel electrophoresis, we showed that PP14, as well as its alternative splice variant PP14.2, binds to both alpha(2)M and methylamine-activated (MA)-alpha(2)M. Cross-competition studies demonstrated that the variants compete for binding to alpha(2)M. PP14 bound to alpha(2)M and MA-alpha(2)M with K(d) values of 167+/-70 and 221+/-56 nM (means+/-S.D.) respectively, as determined by surface plasmon resonance. Significantly, the addition of alpha(2)M or MA-alpha(2)M to a T-cell proliferation assay strongly potentiated the inhibitory capacity of PP14. On the basis of these findings, alpha(2)M emerges as the first serum protein that can physically associate with, and thereby regulate, PP14. Moreover, this represents the first documented interaction between the protein carrier alpha(2)M and a lipocalin protein.
Riely
G J
GJ
Department of Pathology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Rachmilewitz
J
J
Koo
P H
PH
Tykocinski
M L
ML
D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D000071816:Glycodelin; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000378:metabolism*; D007700:Kinetics; D008744:Methylamines / Q000494:pharmacology; D010949:Plasma / Q000378:metabolism; D011257:Pregnancy Proteins / Q000378:metabolism*; D020033:Protein Isoforms; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000502:physiology*
D000071816:Glycodelin; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D008744:Methylamines; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D000511:alpha-Macroglobulins; D012967:Sodium Dodecyl Sulfate; C027451:methylamine