title: Heparin is an adhesive ligand for the leukocyte integrin Mac-1 (CD11b/CD1).
abstract: Previous studies have demonstrated that the leukocyte integrin Mac-1 adheres to several cell surface and soluble ligands including intercellular adhesion molecule-1, fibrinogen, iC3b, and factor X. However, experiments with Mac-1-expressing transfectants, purified Mac-1, and mAbs to Mac-1 indicate the existence of additional ligands. In this paper, we demonstrate a direct interaction between Mac-1 and heparan sulfate glycans. Heparin affinity resins immunoprecipitate Mac-1, and neutrophils and transfectant cells that express Mac-1 bind to heparin and heparan sulfate, but not to other sulfated glycosaminoglycans. Inhibition studies with mAbs and chemically modified forms of heparin suggest the I domain as a recognition site on Mac-1 for heparin, and suggest that either N- or O-sulfation is sufficient for heparin to bind efficiently to Mac-1. Under conditions of continuous flow in which heparins and E-selectin are cosubstrates, neutrophils tether to E-selectin and form firm adhesions through a Mac-1-heparin interaction.
authors.affiliation: Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Diamond
authors.forename: R
authors.initials: R
authors.lastname: Alon
authors.forename: C A
authors.initials: CA
authors.lastname: Parkos
authors.forename: M T
authors.initials: MT
authors.lastname: Quinn
authors.forename: T A
authors.initials: TA
authors.lastname: Springer
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D006224:Cricetinae; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D008024:Ligands; D016177:Macrophage-1 Antigen; D006493:Heparin