A peptide derived from the intercellular adhesion molecule-2 regulates the avidity of the leukocyte integrins CD11b/CD18 and CD11c/CD18.

Abstract

Abstract. ~2 integrin (CDlla,b,c/CD18)-mediated cell adhesion is required for many leukocyte functions. Under normal circumstances, the integrins are nonadhesive, and become adhesive for their cell surface ligands, the intercellular adhesion molecules (ICAMs), or soluble ligands such as fibrinogen and iC3b, when leukocytes are activated. Recently, we defined a peptide derived from ICAM-2, which specifically binds to purified CDlla/CD18. Furthermore, this peptide strongly induces T cell aggregation mainly mediated by CDlla/CD18-ICAM-1 interaction, and natural killer cell cytotoxicity. In the present study, we show that the same ICAM-2 peptide also avidly binds to purified CDllb/CD18, but not to CDllc/CD18. This binding can be blocked by the CD1 lb antibody OKM10. The peptide strongly stimulates CDllb/CD18-ICAM-l-mediated cell aggregations of the monocytic cell lines THP-1 and U937. The aggregations are energy and divalent cation-dependent. The ICAM-2 peptide also induces CDllb/CD18 and CDllc/CD18-mediated binding of THP-1 cells to fibrinogen and iC3b coated on plastic. These findings indicate that in addition to induction of CDlla/CD18-mediated cell adhesion, the ICAM-2 peptide may also serve as a "trigger" for high avidity ligand binding of other ~2 integrins.

Identification of a Novel Integrin αMβ2 Binding Site in CCN1 (CYR61), a Matricellular Protein Expressed in Healing Wounds and Atherosclerotic Lesions

“…Indeed, several ␣ M ␤ 2 binding sequences have been identified (Table II), including the P1 and P2 sequences in the fibrinogen ␥ chain (25,36) and a nine-residue sequence in the coagulation factor X (37). In addition, a 22-residue sequence in intercellular adhesion molecule-2 binds to both ␣ M ␤ 2 and ␣ L ␤ 2 (38,39), and a LLG-C4 biscyclic nonapeptide derived from phage display screening interacts with ␣ M ␤ 2 , ␣ L ␤ 2 , and ␣ X ␤ 2 (40). Our newly identified CCN1-H2 sequence exhibits no apparent homology with these ␣ M ␤ 2 binding motifs other than a pair of basic amino acid residues is present in both P1 and P2 of fibrinogen, the factor X sequence, and CCN1-H2.…”

The Leukocyte Integrins

“…Two functional states of the crystallized ␣ M I domain indicate a basis for changes in conformation (17,26,27). Avidity modulation involving clustering of ␣ M ␤ 2 or cell spreading also occurs (1,29,30,58). L-plastin, an actin-organizing protein, regulates ␣ M ␤ 2 on human monocytes and neutrophils based on experiments with cell-permeant peptides (59).…”

Identification of a Negatively Charged Peptide Motif within the Catalytic Domain of Progelatinases That Mediates Binding to Leukocyte β2 Integrins

“…Cell Culture-The human HT1080 fibrosarcoma and THP-1 and Jurkat leukemic lines were obtained from ATCC and maintained as described previously (11,25,28). OCI/AML-3, derived from the primary blasts of an AML patient (29), was maintained in 10% fetal bovine serum/RPMI supplemented with L-glutamine, penicillin, and streptomycin.…”