title: The macrophage alphaMbeta2 integrin alphaM lectin domain mediates the phagocytosis of chilled platelets.
abstract: alpha(M)beta(2) integrin receptors on myeloid cells mediate the adhesion or uptake of diverse ligands. Ligand binding occurs in the alpha(M) chain, which is composed of an I domain and a lectin domain. The alpha(M) I domain binds iC3b, fibrinogen, intercellular adhesion molecule-1, and other ligands and mediates the adhesion of neutrophils to platelet glycoprotein Ibalpha (GPIbalpha). alpha(M)beta(2) also recognizes beta-GlcNAc residues on GPIbalpha that are clustered on platelets after cooling. The phagocytosis of chilled platelets could be reconstituted when Chinese hamster ovary cells were transfected with alpha(M)beta(2). Replacement of the I domain or the lectin domain of the alpha(M) chain with the corresponding domain from the alpha(X) chain (p150) revealed that the activity of the alpha(M)beta(2) integrin toward chilled platelets resides within the lectin domain and does not require the I domain. Additional evidences for this conclusion are: 1) Sf9 cells expressing solely the alpha(M) lectin domain bound chilled platelets, and 2) soluble recombinant alpha(M) lectin domain inhibited the phagocytosis of chilled platelets by alpha(M)beta(2)-expressing THP-1 cells, whereas I domain substrates showed no inhibitory effect. Therefore chilled platelets are removed from blood by an interaction between beta-GlcNAc residues on clustered GPIbalpha and the lectin domain of alpha(M) chain of the alpha(M)beta(2) integrin, distinguishing this interaction from those mediated by the alpha(M) I domain.
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Josefsson
authors.forename: Harry H
authors.initials: HH
authors.lastname: Gebhard
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Stossel
authors.forename: John H
authors.initials: JH
authors.lastname: Hartwig
authors.forename: Karin M
authors.initials: KM
authors.lastname: Hoffmeister
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D016466:CHO Cells; D002478:Cells, Cultured; D003080:Cold Temperature; D006224:Cricetinae; D006801:Humans; D037102:Lectins / Q000494:pharmacology / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D010587:Phagocytosis / Q000502:physiology*
chemical_list: D037102:Lectins; D016177:Macrophage-1 Antigen