Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses

It is currently thought that immune responses are initiated by pathogen-associated molecular patterns or by tissue-derived danger/alarm signals. Here, we propose that these two groups of molecules might not be mutually exclusive. Many of them might be part of an evolutionarily ancient alert system in which the hydrophobic portions of biological molecules act, when exposed, as universal damage-associated molecular patterns to initiate repair, remodelling and immunity.

[1]  G. Núñez,et al.  Cell death and immunity: NODs: intracellular proteins involved in inflammation and apoptosis , 2003, Nature Reviews Immunology.

[2]  M. Delseny,et al.  Inducibility by pathogen attack and developmental regulation of the rice Ltp1 gene , 2002, Plant Molecular Biology.

[3]  K. Reid,et al.  Structures and functions of mammalian collectins. , 2001, Results and problems in cell differentiation.

[4]  M. Krieger Molecular flypaper and atherosclerosis: structure of the macrophage scavenger receptor. , 1992, Trends in biochemical sciences.

[5]  S. Iwanaga,et al.  The role of hemolymph coagulation in innate immunity. , 1996, Current opinion in immunology.

[6]  Jerome F. Strauss,et al.  The Extra Domain A of Fibronectin Activates Toll-like Receptor 4* , 2001, The Journal of Biological Chemistry.

[7]  M. Koch,et al.  Biological activities of lipopolysaccharides are determined by the shape of their lipid A portion. , 2000, European journal of biochemistry.

[8]  A. Clarke,et al.  Molecular chaperones: physical and mechanistic properties. , 1995, Essays in biochemistry.

[9]  J. Morser,et al.  RORα1 and RORα4 suppress TNF‐α‐induced VCAM‐1 and ICAM‐1 expression in human endothelial cells , 2004, FEBS letters.

[10]  J. Martín Protein folding assisted by the GroEL/GroES chaperonin system. , 1998, Biochemistry. Biokhimiia.

[11]  G. Retzinger,et al.  Adsorption of fibrinogen to droplets of liquid hydrophobic phases. Functionality of the bound protein and biological implications. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[12]  S. Akira,et al.  Toll-like receptors. , 2003, Annual review of immunology.

[13]  K. Fukase,et al.  Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity. , 2000, European journal of biochemistry.

[14]  M. Wurfel,et al.  Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14 , 1994, The Journal of experimental medicine.

[15]  N. Sinha,et al.  Electrostatics in protein binding and function. , 2002, Current protein & peptide science.

[16]  G. Waksman,et al.  Structural basis of chaperone function and pilus biogenesis. , 1999, Science.

[17]  S. Smedt,et al.  Hyaluronan: Preparation, Structure, Properties, and Applications , 1999 .

[18]  N. Surolia,et al.  Titration calorimetric studies to elucidate the specificity of the interactions of polymyxin B with lipopolysaccharides and lipid A. , 1996, The Biochemical journal.

[19]  A. Devitt,et al.  CD14 and apoptosis , 1999, Apoptosis.

[20]  Daniel Hanau,et al.  Heat-shock proteins as activators of the innate immune system. , 2002, Trends in immunology.

[21]  J. Silver,et al.  Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. , 1996, Immunity.

[22]  K. Matsumoto,et al.  Oxidized LDL-induced NF-kappa B activation and subsequent expression of proinflammatory genes are defective in monocyte-derived macrophages from CD36-deficient patients. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[23]  S. Wright,et al.  Soluble CD14 Mediates Efflux of Phospholipids from Cells1 , 2001, The Journal of Immunology.

[24]  Igor N. Berezovsky,et al.  Protein Structure and Folding: A New Start , 2001, Journal of biomolecular structure & dynamics.

[25]  P. Savage,et al.  Editing of CD1d-Bound Lipid Antigens by Endosomal Lipid Transfer Proteins , 2004, Science.

[26]  N. Brot,et al.  C-Reactive Protein Binds to Apoptotic Cells, Protects the Cells from Assembly of the Terminal Complement Components, and Sustains an Antiinflammatory Innate Immune Response , 2000, The Journal of experimental medicine.

[27]  J. Kourie,et al.  Ion channel formation and membrane‐linked pathologies of misfolded hydrophobic proteins: The role of dangerous unchaperoned molecules , 2002, Clinical and experimental pharmacology & physiology.

[28]  P. Williamson,et al.  Membrane phospholipid asymmetry as a determinant of erythrocyte recognition by macrophages. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Barrick,et al.  Sequence analysis of an artificial family of RNA‐binding peptides , 2002, Protein science : a publication of the Protein Society.

[30]  B. Bennett,et al.  The Adjuvant Activity of Nonionic Block Polymer Surfactants , 1986, Scandinavian journal of immunology.

[31]  C. V. van Oss Phagocytosis as a surface phenomenon. , 1978, Annual review of microbiology.

[32]  T. Muta,et al.  Essential roles of CD14 and lipopolysaccharide-binding protein for activation of toll-like receptor (TLR)2 as well as TLR4 Reconstitution of TLR2- and TLR4-activation by distinguishable ligands in LPS preparations. , 2001, European journal of biochemistry.

[33]  S. Wright,et al.  Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids. , 1997, The Journal of clinical investigation.

[34]  P. Borst,et al.  ABC transporters in lipid transport. , 2000, Biochimica et biophysica acta.

[35]  T. Ogawa,et al.  Chemical structure and immunobiological activity of lipid A from Prevotella intermedia ATCC 25611 lipopolysaccharide , 2003, FEBS letters.

[36]  G. Tannock,et al.  Cell Wall-Anchored CshA Polypeptide (259 Kilodaltons) in Streptococcus gordonii Forms Surface Fibrils That Confer Hydrophobic and Adhesive Properties , 1999, Journal of bacteriology.

[37]  Antibody-independent activation of the complement system by mitochondria is mediated by cardiolipin. , 1988, The Biochemical journal.

[38]  R. S. Kiss,et al.  Structure-function relationships of apolipoprotein A-I: a flexible protein with dynamic lipid associations , 2003, Current opinion in lipidology.

[39]  R. Levy,et al.  The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding. , 2003, Structure.

[40]  Charles A. Janeway,et al.  Decoding the Patterns of Self and Nonself by the Innate Immune System , 2002, Science.

[41]  P. Horowitz,et al.  The Chaperonin GroEL Is Destabilized by Binding of ADP (*) , 1995, The Journal of Biological Chemistry.

[42]  P. Goloubinoff,et al.  Review: mechanisms of disaggregation and refolding of stable protein aggregates by molecular chaperones. , 2001, Journal of structural biology.

[43]  S. White,et al.  Critical Role of Lipid Composition in Membrane Permeabilization by Rabbit Neutrophil Defensins* , 1997, The Journal of Biological Chemistry.

[44]  P. Williamson,et al.  Phosphatidylserine expression and phagocytosis of apoptotic thymocytes during differentiation of monocytic cells , 2003, Journal of leukocyte biology.

[45]  H. Hammad,et al.  Peroxisome Proliferator-Activated Receptor γ Inhibits the Migration of Dendritic Cells: Consequences for the Immune Response1 , 2003, The Journal of Immunology.

[46]  S. Pietschmann,et al.  Host defence capacities of pulmonary surfactant: evidence for ‘non‐surfactant’ functions of the surfactant system , 1994, European journal of clinical investigation.

[47]  M. Olson,et al.  C1q binding and C1 activation by various isolated cellular membranes. , 1983, Journal of immunology.

[48]  T. Hartung,et al.  Lipopolysaccharide (LPS)-Binding Protein Mediates LPS Detoxification by Chylomicrons 1 , 2003, The Journal of Immunology.

[49]  N. Key,et al.  CD4+ T Cell Response to Factor VIII in Hemophilia A, Acquired Hemophilia, and Healthy Subjects , 1999, Thrombosis and Haemostasis.

[50]  G. Thorbecke,et al.  Tolerance in adult rabbits by repeated non-immunogenic doses of bovine serum albumin. , 1967, Immunology.

[51]  P. Moseley,et al.  Activation of heat-shock response by an adenovirus is essential for virus replication , 2000, Nature.

[52]  T. Theander,et al.  Malaria-Induced Acquisition of Antibodies to Plasmodium falciparum Variant Surface Antigens , 2002, Infection and Immunity.

[53]  M. Gaestel,et al.  Analysis of the Interaction of Small Heat Shock Proteins with Unfolding Proteins* , 2003, The Journal of Biological Chemistry.

[54]  D. Vance,et al.  Cholesterol in the year 2000. , 2000, Biochimica et biophysica acta.

[55]  D. Persing,et al.  Structure-Activity Relationship of Synthetic Toll-like Receptor 4 Agonists* , 2004, Journal of Biological Chemistry.

[56]  R. Huber,et al.  Crystal structure of a coagulogen, the clotting protein from horseshoe crab: a structural homologue of nerve growth factor. , 1996, The EMBO journal.

[57]  Michael Rehli,et al.  Novel Signal Transduction Pathway Utilized by Extracellular HSP70 , 2002, The Journal of Biological Chemistry.

[58]  Z Dembic,et al.  Immune system protects integrity of tissues. , 2000, Molecular immunology.

[59]  M. Shima,et al.  Role of activation of the coagulation factor VIII in interaction with vWf, phospholipid, and functioning within the factor Xase complex. , 1999, Trends in cardiovascular medicine.

[60]  C. Janeway Approaching the asymptote? Evolution and revolution in immunology. , 1989, Cold Spring Harbor symposia on quantitative biology.

[61]  I. Ofek,et al.  Bacterial Adhesion to Cells and Tissues , 1994, Springer US.

[62]  R. Huber,et al.  The 2.0-Å crystal structure of tachylectin 5A provides evidence for the common origin of the innate immunity and the blood coagulation systems , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[63]  A. Jonas,et al.  Apolipoprotein A-II Modulates the Binding and Selective Lipid Uptake of Reconstituted High Density Lipoprotein by Scavenger Receptor BI* , 2001, The Journal of Biological Chemistry.

[64]  H. Harris,et al.  Induction of cytokine tolerance requires internalization of Chylomicron-Bound LPS into hepatocytes. , 2003, The Journal of surgical research.

[65]  P. Matzinger Tolerance, danger, and the extended family. , 1994, Annual review of immunology.

[66]  U. Bonas,et al.  Plant disease resistance triggered by pathogen-derived molecules: refined models of specific recognition. , 2002, Current opinion in microbiology.

[67]  M. Koch,et al.  Supramolecular structure of lipopolysaccharide and free lipid A under physiological conditions as determined by synchrotron small-angle X-ray diffraction. , 1989, European journal of biochemistry.

[68]  T. Ahrens,et al.  Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 , 2002, The Journal of experimental medicine.

[69]  A. Osterhaus,et al.  Vγ9Vδ2 T cells recovered from eyes of patients with Behçet's disease recognize non-peptide prenyl pyrophosphate antigens , 2002, Journal of Neuroimmunology.

[70]  M. Ziegler,et al.  Insect immune activation by apolipophorin III is correlated with the lipid-binding properties of this protein. , 2001, Biochemistry.

[71]  W. Weigle,et al.  Studies on the induction of immunologic unresponsiveness. 3. Antigen form and mouse strain variation. , 1969, Journal of immunology.

[72]  S. Kiechl,et al.  Toll-like receptor 4 and atherogenesis , 2003, Annals of medicine.

[73]  Douglas T. Golenbock,et al.  Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus , 2000, Nature Immunology.

[74]  A. Minton,et al.  The Influence of Macromolecular Crowding and Macromolecular Confinement on Biochemical Reactions in Physiological Media* , 2001, The Journal of Biological Chemistry.

[75]  M. Walport,et al.  Role of Surfactant Proteins A, D, and C1q in the Clearance of Apoptotic Cells In Vivo and In Vitro: Calreticulin and CD91 as a Common Collectin Receptor Complex1 , 2002, The Journal of Immunology.

[76]  R. Hunter,et al.  The adjuvant activity of nonionic block polymer surfactants. I. The role of hydrophile-lipophile balance. , 1981, Journal of immunology.

[77]  S. Bhakdi,et al.  Isolation and characterization of a complement-activating lipid extracted from human atherosclerotic lesions , 1990, The Journal of experimental medicine.

[78]  D. Lipsker,et al.  Endotoxin‐free heat‐shock protein 70 fails to induce APC activation , 2002, European journal of immunology.

[79]  B. Bloom,et al.  Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. , 1999, Science.

[80]  J. Weckesser,et al.  Influence of the supramolecular structure of free lipid A on its biological activity. , 1993, European journal of biochemistry.

[81]  W. Weigle,et al.  Studies on the induction of immunologic unresponsiveness. II. Kinetics. , 1967, Journal of immunology.

[82]  K. Miyake,et al.  Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. , 2002, Biochemical and biophysical research communications.

[83]  U. Shankavaram,et al.  Role of macrophages in vascular tissue remodelling. , 1997, Transplant immunology.

[84]  D. Steinberg,et al.  Evidence that the lipid moiety of oxidized low density lipoprotein plays a role in its interaction with macrophage receptors. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[85]  S. Wood,et al.  The physiological structure of human C-reactive protein and its complex with phosphocholine. , 1999, Structure.

[86]  D. Ferrandon,et al.  Cutting Edge: The Toll Pathway Is Required for Resistance to Gram-Positive Bacterial Infections in Drosophila1 , 2002, The Journal of Immunology.

[87]  P. Williamson,et al.  CD14 is a component of multiple recognition systems used by macrophages to phagocytose apoptotic lymphocytes , 1999, Cell Death and Differentiation.

[88]  D. Golenbock,et al.  Cutting Edge: The Immunostimulatory Activity of the Lung Surfactant Protein-A Involves Toll-Like Receptor 41 , 2002, The Journal of Immunology.

[89]  A. D. McLachlan,et al.  Solvation energy in protein folding and binding , 1986, Nature.

[90]  J. Berman,et al.  CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. , 2002, The American journal of pathology.

[91]  Francis C. Neuhaus,et al.  A Continuum of Anionic Charge: Structures and Functions of d-Alanyl-Teichoic Acids in Gram-Positive Bacteria , 2003, Microbiology and Molecular Biology Reviews.

[92]  M. Koch,et al.  The generalized endotoxic principle , 2003, European journal of immunology.

[93]  M. Steinberg,et al.  Pathophysiology of sickle cell disease: role of cellular and genetic modifiers. , 2001, Seminars in hematology.

[94]  S. Wright,et al.  Neutralization and Transfer of Lipopolysaccharide by Phospholipid Transfer Protein (*) , 1996, The Journal of Biological Chemistry.

[95]  J. Lieske,et al.  Adhesion of uric acid crystals to the surface of renal epithelial cells. , 2000, American journal of physiology. Renal physiology.

[96]  H. Sano,et al.  A novel type of binding specificity to phospholipids for rat mannose‐binding proteins isolated from serum and liver , 1997, FEBS letters.

[97]  P. Adams,et al.  Conformational variability in the refined structure of the chaperonin GroEL at 2.8 Å resolution , 1995, Nature Structural Biology.

[98]  C. J. Oss,et al.  Phagocytosis as a Surface Phenomenon , 1978 .

[99]  A. Molina,et al.  Developmental and pathogen-induced expression of three barley genes encoding lipid transfer proteins. , 1993, The Plant journal : for cell and molecular biology.

[100]  S. Akira,et al.  Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8 , 2004, Science.

[101]  A. Aderem,et al.  Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility , 2003, Nature Immunology.

[102]  Ping-yuan Wang,et al.  CD14-dependent Internalization and Metabolism of Extracellular Phosphatidylinositol by Monocytes* , 1999, The Journal of Biological Chemistry.

[103]  D. Davies,et al.  Leucine-rich repeats and pathogen recognition in Toll-like receptors. , 2003, Trends in immunology.

[104]  E Y Jones,et al.  MHC class I and class II structures. , 1997, Current opinion in immunology.

[105]  S. Gordon,et al.  Class A scavenger receptors and the phagocytosis of apoptotic cells. , 1998, Biochemical Society Transactions.

[106]  Stefania Gallucci,et al.  Natural adjuvants: Endogenous activators of dendritic cells , 1999, Nature Medicine.

[107]  R. Zidovetzki,et al.  Amphipathic beta structure of a leucine-rich repeat peptide. , 1991, The Journal of biological chemistry.

[108]  S. Gordon,et al.  Is the class A macrophage scavenger receptor (SR-A) multifunctional? - The mouse's tale. , 2001, The Journal of clinical investigation.

[109]  Yung-Hua Li,et al.  Quorum sensing and biofilm formation in Streptococcal infections. , 2003, The Journal of clinical investigation.

[110]  S. Lau,et al.  Clinical Spectrum of Paradoxical Deterioration During Antituberculosis Therapy in Non-HIV-Infected Patients , 2002, European Journal of Clinical Microbiology and Infectious Diseases.

[111]  V. Fadok,et al.  The phosphatidylserine receptor: a crucial molecular switch? , 2001, Nature Reviews Molecular Cell Biology.

[112]  James E. Evans,et al.  Molecular identification of a danger signal that alerts the immune system to dying cells , 2003, Nature.

[113]  A. Hofmann,et al.  Physicochemical properties of bile acids and their relationship to biological properties: an overview of the problem. , 1984, Journal of lipid research.

[114]  N. Sinclair,et al.  Co‐Stimulation and Co‐Inhibition: Equal Partners in Regulation , 1996, Scandinavian journal of immunology.

[115]  Raz Jelinek,et al.  Lipid binding and membrane penetration of polymyxin B derivatives studied in a biomimetic vesicle system. , 2003, Biochemical Journal.

[116]  C. Janeway,et al.  Innate immune recognition. , 2002, Annual review of immunology.

[117]  T. Lawrence,et al.  Anti-inflammatory lipid mediators and insights into the resolution of inflammation , 2002, Nature Reviews Immunology.

[118]  L. Kwak,et al.  Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by β-Defensin 2 , 2002, Science.

[119]  A. Pain,et al.  Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells , 1999, Nature.

[120]  T. Kodama,et al.  Scavenger receptor family proteins: roles for atherosclerosis, host defence and disorders of the central nervous system , 1998, Cellular and Molecular Life Sciences CMLS.

[121]  D. Golenbock,et al.  Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. , 1991, The Journal of biological chemistry.

[122]  R. Schlegel,et al.  The Central Role of Phosphatidylserine in the Phagocytosis of Apoptotic Thymocytes , 2000, Annals of the New York Academy of Sciences.

[123]  F. Hartl,et al.  Roles of molecular chaperones in cytoplasmic protein folding. , 2000, Seminars in cell & developmental biology.

[124]  P S Kim,et al.  Structural characterization of the human respiratory syncytial virus fusion protein core. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[125]  D. Ganea,et al.  Prostaglandin E2 inhibits TNF production in murine bone marrow-derived dendritic cells. , 2003, Cellular immunology.