Activation of natural killer cell migration by leukocyte integrin-binding peptide from intracellular adhesion molecule-2 (ICAM-2).
Intracellular adhesion molecule-2 (ICAM-2), one of the ligands of CD11a/CD18 (LFA-1), is mainly expressed on endothelial and hematopoietic cells. The biological significance of ICAM-2 has remained unclear. Previous findings have shown that a peptide from ICAM-2, spanning residues 21-42 from the first immunoglobulin domain, enhances natural killer (NK) cell cytotoxicity and induces T cell aggregation. We have now studied the effect of the same ICAM-2 peptide on NK cell migration in the Boyden chamber assay. The peptide significantly increased NK cell migration up to 215 +/- 21%, as compared to migration of control cells (100%), and the induction was inhibited by anti-CD11a monoclonal antibodies. The ICAM-2 peptide also induced polymerization of F-actin at the leading edge of migratory NK cells. Cross-linking of CD11a/CD18 receptors with anti-CD11a or anti-CD18 monoclonal antibodies and secondary antibodies resulted in receptor recycling, increased migration, and actin polymerization, but led to slight inhibition of cytotoxicity. The ICAM-2 peptide did not induce such a receptor recycling. Phosphotyrosine immunoblotting experiments showed that the ICAM-2 peptide increased the phosphorylation of 150- and 35-kDa proteins. During cross-linking with antibodies, only the 150-kDa protein showed increased phosphorylation. The results show that depending on the type of CD11a/CD18 receptor ligation different kinds of signals are transduced in NK cells. These signals may either trigger only locomotion, or both locomotion and cytotoxicity. Based on these findings, a major function for ICAM-2 on endothelium may be triggering of migration of adhering leukocytes.
Somersalo
K
K
Department of Pathology, University of Helsinki, Finland.
Carpén
O
O
Saksela
E
E
Gahmberg
C G
CG
Nortamo
P
P
Timonen
T
T
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D015703:Antigens, CD; D018821:CD18 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002470:Cell Survival / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D010446:Peptide Fragments; D010716:Phosphatidylinositols; D014443:Tyrosine; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases