Occupancy of CD11b/CD18 (Mac-1) divalent ion binding site(s) induces leukocyte adhesion.

The group of leukocyte integrins CD11a-c/CD18 coordinate disparate adhesion reactions in the immune system through a regulated process of ligand recognition. The participation of the receptor divalent ion binding site(s) in this mechanism of ligand binding has been investigated. As compared with other divalent cations, Mn2+ ions have the unique property to dramatically stimulate the adhesive functions of the leukocyte integrin CD11b/CD18 (Mac-1), expressed on myelo-monocytic cells. This is reflected in a three- to fivefold increased early monocyte adhesion (less than 20 min) to resting, unperturbed endothelial cells, and increased association of CD11b/CD18 with its soluble ligands fibrinogen and factor X. CD11b/CD18 ligand recognition in the presence of Mn2+ ions is specific, time and concentration dependent, and inhibited by anti-CD11b mAb. At variance with Ca(2+)-containing reactions where CD11b/CD18 functions as an inducible receptor activated by adenine nucleotides or chemoattractants, Mn2+ ions induce per se a constitutive maximal ligand binding capacity of CD11b/CD18, that is not further modulated by cell stimulation. Rather than quantitative changes in surface density, Mn2+ ions increase the affinity of CD11b/CD18 for its complementary ligands up to 10-fold, as judged by Scatchard plot analysis of receptor:ligand interaction under these conditions. Furthermore, monocyte exposure to Mn2+ ions induces the expression of activation-dependent neo-antigenic epitopes on CD11b/CD18, selectively recognized by mAb 7E3. These data suggest that in addition to cell-activating stimuli, favorable engagement of divalent ion binding site(s) can provide an alternative pathway to rapidly regulate the receptor affinity of leukocyte integrins.

• Publication year

  1991

• Venue

  Journal of Immunology

• Publication date

  1991-09-15

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.4049/jimmunol.147.6.1891PMID 1890307
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Ligands "activate" integrin alpha IIb beta 3 (platelet GPIIb-IIIa).

  1991cited by this paper
• Leukocyte‐Cell Adhesion: A Molecular Process Fundamental in Leukocyte Physiology

  1990cited by this paper
• Structure and function of the leukocyte adhesion molecules CD11/CD18.

  1990cited by this paper
• Membrane Proteins Involved in Phagocyte Adherence to Endothelium

  1990cited by this paper
• A beta 3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation.

  1990cited by this paper
• Structure and Function of Leukocyte Integrins

  1990cited by this paper
• Cation-dependent changes in the binding specificity of the platelet receptor GPIIb/IIIa.

  1990cited by this paper
• Leukocyte adhesion to endothelium in inflammation.

  1990cited by this paper
• Identification of a monoclonal antibody against platelet GPIIb that interacts with a calcium-binding site and induces aggregation.

  1990cited by this paper
• Characterization of monocyte adherence to human macrovascular and microvascular endothelial cells.

  1990cited by this paper
• Signal transduction initiated by extracellular nucleotides regulates the high affinity ligand recognition of the adhesive receptor CD11b/CD18.

  1990cited by this paper
• The ligand binding site of the platelet integrin receptor GPIIb-IIIa is proximal to the second calcium binding domain of its alpha subunit.

  1990cited by this paper
• High molecular weight kininogen inhibits fibrinogen binding to cytoadhesins of neutrophils and platelets

  1989cited by this paper
• T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1

  1989cited by this paper
• Transient adhesion of neutrophils to endothelium

  1989cited by this paper
• Regulated expression of Mg2+ binding epitope on leukocyte integrin alpha subunits.

  1989cited by this paper
• Neutrophil adherence to human endothelium in vitro occurs by CDw18 (Mo1, MAC-1/LFA-1/GP 150,95) glycoprotein-dependent and -independent mechanisms.

  1988cited by this paper
• Increased surface expression of CD11b/CD18 (Mac-1) is not required for stimulated neutrophil adherence to cultured endothelium.

  1988cited by this paper
• Determination of manganese in biological materials by electrothermal atomic absorption spectrometry: a review.

  1988cited by this paper
• Dissociation between increased surface expression of gp165/95 and homotypic neutrophil aggregation.

  1988cited by this paper
• Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion.

  1988cited by this paper
• The saturable high affinity association of factor X to ADP-stimulated monocytes defines a novel function of the Mac-1 receptor.

  1988cited by this paper
• A monoclonal antibody reacting with distinct adhesion molecules defines a transition in the functional state of the receptor CD11b/CD18 (Mac-1).

  1988cited by this paper
• Induction of fibroblast spreading by Mn2+: a possible role for unusual binding sites for divalent cations in receptors for proteins containing Arg-Gly-Asp.

  1988cited by this paper
• Stimulation of human neutrophil adhesive properties by adenine nucleotides.

  1988cited by this paper
• Regulation of the fibronectin receptor affinity by divalent cations.

  1988cited by this paper
• Oligospecificity of the cellular adhesion receptor Mac-1 encompasses an inducible recognition specificity for fibrinogen

  1988cited by this paper
• ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells

  1988cited by this paper
• Insulin stimulates a novel Mn2+-dependent cytosolic serine kinase in rat adipocytes.

  1987cited by this paper
• Integrins: a family of cell surface receptors.

  1987cited by this paper
• New perspectives in cell adhesion: RGD and integrins.

  1987cited by this paper
• Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface.

  1987cited by this paper
• Identification of a 160,000 dalton platelet membrane protein that mediates the initial divalent cation-dependent adhesion of platelets to collagen.

  1986cited by this paper
• Manganese-dependent cell-substratum adhesion.

  1984cited by this paper
• Inhibition of phagocytosis of complement C3- or immunoglobulin G-coated particles and of C3bi binding by monoclonal antibodies to a monocyte-granulocyte membrane glycoprotein (Mol).

  1983cited by this paper
• Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies.

  1983cited by this paper
• Degranulation, membrane addition, and shape change during chemotactic factor-induced aggregation of human neutrophils

  1982cited by this paper
• Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds.

  1978cited by this paper

• Immunomodulatory Effects of Selected Non-Nutritive Bioactive Compounds and Their Role in Optimal Nutrition

  2025cites this paper
• Anticancer immune responses are hindered by cis interaction of inhibitory checkpoint SIRPα.

  2025cites this paper
• FGF1 Suppresses Allosteric Activation of β3 Integrins by FGF2: A Potential Mechanism of Anti-Inflammatory and Anti-Thrombotic Action of FGF1

  2024cites this paper
• A myristoylated alanine-rich C-kinase substrate (MARCKS) inhibitor peptide attenuates neutrophil outside-in β2-integrin activation and signaling

  2023cites this paper
• Increased Dietary Manganese Impairs Neutrophil Extracellular Trap Formation Rendering Neutrophils Ineffective at Combating Staphylococcus aureus

  2022cites this paper
• Pro-Inflammatory Chemokines CCL5, CXCL12, and CX3CL1 Bind to and Activate Platelet Integrin αIIbβ3 in an Allosteric Manner

  2022cites this paper
• Manganese homeostasis at the host-pathogen interface and in the host immune system.

  2021cites this paper
• The impact of metal availability on immune function during infection.

  2021cites this paper
• Manganese-Doped Silica-Based Nanoparticles Promote the Efficacy of Antigen-Specific Immunotherapy

  2021cites this paper
• A Novel Genetic Model of Constitutively Active Integrin CD11b/ CD18

  2020cites this paper
• A Genetic Model of Constitutively Active Integrin CD11b/CD18

  2020cites this paper
• Circulating microvesicles as mediators of acute pulmonary vascular inflammation

  2020cites this paper
• Cytoplasmic Tails of and p 7 Integrins Differentially Regulate LFA-1 Function in K 562 Cells

  2017cites this paper
• Mitotic Cortical Waves Predict Future Division Sites by Encoding Positional and Size Information.

  2017cites this paper
• Coronin 1A, a novel player in integrin biology, controls neutrophil trafficking in innate immunity.

  2017cites this paper
• The integrin αL leg region controls the Mg/EGTA mediated activation of LFA-1.

  2015cites this paper
• Identification of HETE isoforms produced by activated platelets and study of their roles within the vasculature.

  2015cites this paper
• Bordetella adenylate cyclase toxin is a unique ligand of the integrin complement receptor 3

  2015cites this paper
• Studies of SIRPα-mediated regulation of neutrophil functions

  2014cites this paper
• Structural features that affect β2 integrin expression and regulation of adhesion

  2013cites this paper
• Agonist leukadherin-1 increases CD11b/CD18-dependent adhesion via membrane tethers.

  2013cites this paper
• Small molecule agonists of integrin CD11b/CD18 do not induce global conformational changes and are significantly better than activating antibodies in reducing vascular injury.

  2013cites this paper
• Structures and interactions of the leukocyte-specific integrins cytoplasmic tails

  2013cites this paper
• Pericytes Regulate Vascular Basement Membrane Remodeling and Govern Neutrophil Extravasation during Inflammation

  2012cites this paper
• functional unit on monocytic cells Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a

  2011cites this paper
• The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL–C3G complex and activating Rap1 at the leading edge

  2011cites this paper
• Small Molecule–Mediated Activation of the Integrin CD11b/CD18 Reduces Inflammatory Disease

  2011cites this paper
• Molecular mechanisms of signal transduction in neutrophil chemotaxis

  2011cites this paper
• Activation of human neutrophil Mac-1 by anion substitution.

  2009cites this paper
• Glycosyltransferase‐programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration

  2009cites this paper
• Urokinase-type Plasminogen Activator Receptor Induces Conformational Changes in the Integrin αMβ2 Headpiece and Reorientation of Its Transmembrane Domains*

  2008cites this paper
• The Atypical Zeta (ζ) Isoform of Protein Kinase C Regulates CD11b/CD18 Activation in Human Neutrophils

  2008cites this paper
• Novel Tools for Functional Analysis of CD11c: Activation‐Specific, Activation‐Independent, and Activating Antibodies

  2007cites this paper
• Interaction between single molecules of Mac-1 and ICAM-1 in living cells: an atomic force microscopy study.

  2007cites this paper
• A Structural Hypothesis for the Transition between Bent and Extended Conformations of the Leukocyte β2 Integrins*

  2007cites this paper
• DIVALENT CATION-INDUCED REGULATION OF ALPHA 5 BETA 1- FIBRONECTIN INTERACTION FORCE ASSESSED USING ATOMIC FORCE MICROSCOPY

  2007cites this paper
• Fibrinogen and fibrin induce synthesis of proinflammatory cytokines from isolated peripheral blood mononuclear cells

  2007influential citation
• Cell-Surface Association between Progelatinases and beta² Integrins: Role of the Complexes in Leukocyte Migration

  2006cites this paper
• Down-regulation of integrin αMβ2 ligand-binding function by the urokinase-type plasminogen activator receptor

  2006cites this paper
• Down-regulation of integrin alpha M beta 2 ligand-binding function by the urokinase-type plasminogen activator receptor.

  2006cites this paper
• Cell adhesion characteristics of a monocytic cell line derived from rainbow trout, Oncorhynchus mykiss.

  2006cites this paper
• Adhesion molecules in lung diseases

  2004cites this paper
• Promotion of Leukocyte Adhesion by a Novel Interaction Between Vitronectin and the β2 Integrin Mac-1 (αMβ2, CD11b/CD18)

  2004cites this paper
• Neutrophil adhesive contact dependence on impingement force.

  2004cites this paper
• Effects of adsorbed proteins and surface chemistry on foreign body giant cell formation, tumor necrosis factor alpha release and procoagulant activity of monocytes.

  2004cites this paper
• Micromechanical tests of adhesion dynamics between neutrophils and immobilized ICAM-1.

  2004influential citation
• Expression of intercellular adhesion molecule (ICAM)-1 by a subset of astrocytes in Alzheimer disease and some other degenerative neurological disorders

  2004cites this paper
• Ceramide Generation in Situ Alters Leukocyte Cytoskeletal Organization and β2-Integrin Function and Causes Complete Degranulation*

  2002cites this paper
• Gene targeting in hemostasis. Factor X.

  2002cites this paper
• Monocyte and Neutrophil Adhesion Molecule Expression During Acute Hyperglycemia and After Antioxidant Treatment in Type 2 Diabetes and Control Patients

  2002cites this paper
• Signaling Pathways Involved in IL-8-Dependent Activation of Adhesion Through Mac-1

  2002cites this paper
• Mac-1 IL-8-Dependent Activation of Adhesion Signaling Pathways Involved in

  2002cites this paper
• Leukocyte De-Adhesion Requirement for RhoA Kinase Activation in

  2002cites this paper
• Signaling Pathways Involved in IL-8-Dependent Activation of Adhesion Through Mac-11

  2002cites this paper
• Degranulation of Primary and Secondary Granules in Adherent Human Neutrophils

  2002cites this paper
• PEO-like plasma polymerized tetraglyme surface interactions with leukocytes and proteins: in vitro and in vivo studies

  2002cites this paper
• Requirement for RhoA Kinase Activation in Leukocyte De-Adhesion1

  2002cites this paper
• Effects of Staphylococcus aureus on human keratinocytes.

  2002cites this paper
• Interface Between Inflammation and Coagulation

  2001cites this paper
• The effects of surface chemistry and adsorbed proteins on monocyte/macrophage adhesion to chemically modified polystyrene surfaces.

  2001cites this paper
• Human Endothelial-Cell Specific Molecule-1 Binds Directly to the Integrin CD11a/CD18 (LFA-1) and Blocks Binding to Intercellular Adhesion Molecule-11

  2001cites this paper
• Adhesion Molecule-1 ( LFA-1 ) and Blocks Binding to Intercellular Binds Directly to the Integrin CD 11 a / CD 18 Human Endothelial-Cell Specific Molecule-1

  2001cites this paper
• Leukocyte Integrin Mac-1 Recruits Toll/Interleukin-1 Receptor Superfamily Signaling Intermediates to Modulate NF-&kgr;B Activity

  2001cites this paper
• Chemoattractants Induce a Rapid and Transient Upregulation of Monocyte α4 Integrin Affinity for Vascular Cell Adhesion Molecule 1 Which Mediates Arrest

  2001cites this paper
• Granulocyte Adhesion to Matrix Proteins and the Effect on the Release of Granule Proteins : Development of a Simple Method and its Application in Experimental and Clinical Studies

  2001cites this paper
• Chemoattractants Induce a Rapid and Transient Upregulation of Monocyte a 4 Integrin Affinity for Vascular Cell Adhesion Molecule 1 Which Mediates Arrest: An Early Step in the Process of Emigration

  2001cites this paper
• Regulation of leukocyte recruitment by polypeptides derived from high molecular weight kininogen

  2001cites this paper
• Mac-1-dependent tyrosine phosphorylation during neutrophil adhesion.

  2001cites this paper
• Bio-PIXEその理論と応用第5章臨床医学への応用 (1) 心筋梗塞, 腎疾患患者の血清中微量元素

  2000cites this paper
• Soluble E-selectin acts in synergy with platelet-activating factor to activate neutrophil beta 2-integrins. Role of tyrosine kinases and Ca2+ mobilization.

  2000cites this paper
• Regulation of the release of eosinophil cationic protein by eosinophil adhesion

  2000cites this paper
• NMR solution structure of the inserted domain of human leukocyte function associated antigen-1.

  2000cites this paper
• Role of the cytoskeleton in rapid activation of CD11b/CD18 function and its subsequent downregulation in neutrophils.

  2000cites this paper
• Fibrinogen binds to integrin alpha(5)beta(1) via the carboxyl-terminal RGD site of the Aalpha-chain.

  2000cites this paper
• Cleaved high molecular weight kininogen binds directly to the integrin CD11b/CD18 (Mac-1) and blocks adhesion to fibrinogen and ICAM-1.

  2000cites this paper
• Differential Roles for αMβ2 Integrin Clustering or Activation in the Control of Apoptosis via Regulation of Akt and ERK Survival Mechanisms

  2000cites this paper
• Simultaneous analysis of eosinophil and neutrophil adhesion to plasma and tissue fibronectin, fibrinogen, and albumin.

  1999cites this paper
• Molecular mechanisms of zinc-dependent leukocyte adhesion involving the urokinase receptor and beta2-integrins.

  1999cites this paper
• Molecular Mechanisms of Zinc-Dependent Leukocyte Adhesion Involving the Urokinase Receptor and β2-Integrins

  1999cites this paper
• Adhesion Receptors Involved in Leukocyte Functions

  1999cites this paper
• Leukocyte adhesion--a fundamental process in leukocyte physiology.

  1999cites this paper
• Leukocyte Adhesion—an Integrated Molecular Process at the Leukocyte Plasma Membrane

  1999cites this paper
• Does soluble intercellular adhesion molecule-1 (ICAM-1) affect neutrophil activation and adhesion following ischaemia-reperfusion?

  1999cites this paper
• Regulation of Leukocyte-Endothelium Interaction by Fibrinogen

  1999cites this paper
• Effects of the presence of the mammary gland on expression of neutrophil adhesion molecules and myeloperoxidase activity in periparturient dairy cows.

  1999cites this paper
• The Role of Cell-Adhesion Molecules in Neurological Disorders

  1998cites this paper
• Molecular identification of the cross-reacting epitope on alphaM beta2 integrin I domain recognized by anti-alphaIIb beta3 monoclonal antibody 7E3 and its involvement in leukocyte adherence.

  1998cites this paper
• Copper and zinc compounds and cell surface interactions

  1998cites this paper
• Molecular Identification of the Cross-reacting Epitope on αMβ2 Integrin I Domain Recognized by Anti-αIIbβ3 Monoclonal Antibody 7E3 and Its Involvement in Leukocyte Adherence*

  1998cites this paper
• β2‐Integrins mediate stable adhesion in collisional interactions between neutrophils and ICAM‐1‐expressing cells

  1998cites this paper
• Enhanced neutrophil and eosinophil adhesion in patients with primary Sjögren's syndrome.

  1998cites this paper
• Dual control by divalent cations and mitogenic cytokines of alpha 4 beta 1 and alpha 5 beta 1 integrin avidity expressed by human hemopoietic cells.

  1998cites this paper
• Two Functional States of the CD11b A-Domain: Correlations with Key Features of Two Mn2+-complexed Crystal Structures

  1998cites this paper
• Expression of the H52 epitope on the β2 subunit is dependent on its interaction with the α subunits of the leukocyte integrins LFA‐1, Mac‐1 and p150,95 and the presence of Ca2+

  1998cites this paper
• Leukocyte integrins and inflammation

  1998cites this paper
• Fibrinogen Activates NF-κB Transcription Factors in Mononuclear Phagocytes

  1998cites this paper
• Two Functional States of the CD11b A-Domain: Correlations with Key Features of Two Mn 2 (cid:49) -complexed Crystal Structures

  1998cites this paper
• Two Signaling Mechanisms for Activation of αMβ2 Avidity in Polymorphonuclear Neutrophils*

  1998cites this paper
• Urokinase Receptor (CD87) Regulates Leukocyte Recruitment via β2 Integrins In Vivo

  1998cites this paper
• Characteristics of Cation Binding to the I Domains of LFA-1 and MAC-1

  1998cites this paper