Cross-linking of the carcinoembryonic antigen-like glycoproteins CD66 and CD67 induces neutrophil aggregation.
The carcinoembryonic Ag (CEA)-like glycoproteins present on human granulocytes have been designated non-specific cross-reacting Ag (NCA). We have recently demonstrated that granulocyte-specific CD66 and CD67 mAb recognize the three originally described NCA. CD66 binds to NCA-160 and NCA-90, whereas CD67 only recognizes NCA-95. As we have shown previously, NCA-160 and NCA-90 present sialylated Lewis-X oligosaccharide Ag (SLex) in a functional way, i.e., these Ag function as (one of many possible) molecules involved in neutrophil binding to the adhesion molecule E-selectin expressed on activated endothelial cells. In this study, we found that a polyclonal anti-CEA antiserum, either as intact Ig or as F(ab')2 fragments, induced neutrophil aggregation. This aggregation response was blocked by CD18 mAb. Neutrophils from a patient severely affected by paroxysmal nocturnal hemoglobinuria completely lacked expression of NCA-95 and NCA-90. The patient's neutrophils repeatedly showed no aggregation on addition of the anti-CEA antiserum. Thus, the presence of the phosphatidylinositol-linked NCA-95/90 seems to be essential for NCA-induced neutrophil activation. Our data indicate that NCA molecules on neutrophils may function via binding to E-selection or an as yet unknown ligand (as mimicked here by an antiserum) and subsequently induce CD18-dependent adhesive properties.
Kuijpers
T W
TW
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
van der Schoot
C E
CE
Hoogerwerf
M
M
Roos
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D000951:Antigens, Neoplasm; D018821:CD18 Antigens; D002272:Carcinoembryonic Antigen / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002449:Cell Aggregation; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D018821:CD18 Antigens; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D007106:Immune Sera; D008562:Membrane Glycoproteins