A role for human Sp alpha as a pattern recognition receptor.
Human Sp alpha is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR) superfamily for which little functional information is available. It is expressed by macrophages present in lymphoid tissues (spleen, lymph node, thymus, and bone marrow), and it binds to myelomonocytic and lymphoid cells, which suggests that it may play an important role in the regulation of the innate and adaptive immune systems. In the present study we show that recombinant human Sp alpha (rSp alpha) binds to the surface of several gram-positive and gram-negative bacterial strains. Competition studies indicated that such binding is mediated by the recognition of lipoteichoic acid (LTA) and lipopolysaccharide (LPS), respectively, through nonoverlapping sites on the Sp alpha molecule. The most conserved part of LPS (2-keto-3-deoxyoctulosonic acid and lipid A) was shown to be involved in the recognition by Sp alpha. Bacterial binding studies using the SRCR domain 1 of Sp alpha showed that this domain retains both the LPS and LTA binding activities, indicating that both bacterial interacting sites are retained in a single SRCR domain. Furthermore, rSp alpha induced aggregation of gram-positive and gram-negative bacteria strains. On the other hand, rSp alpha inhibited tumor necrosis factor-alpha secretion by human monocytes stimulated with LPS or LTA. Binding of Sp alpha to conserved components of bacterial surfaces and modulation of the monocyte response indicate that this molecule is an active constituent of the innate immune response of the host.
Sarrias
Maria-Rosa
MR
Servei d'Immunologia, Hospital Clínic i Provincial de Barcelona, Institut de Investigacions Biomèdiques August Pi i Sunyer, Barcelona 08036, Spain.
Roselló
Sandra
S
Sánchez-Barbero
Fernando
F
Sierra
Josep M
JM
Vila
Jordi
J
Yélamos
José
J
Vives
Jordi
J
Casals
Cristina
C
Lozano
Francisco
F
D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001419:Bacteria / Q000378:metabolism; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D008087:Listeria / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D051116:Receptors, Scavenger / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D051122:Scavenger Receptors, Class B; D017386:Sequence Homology, Amino Acid; D013050:Spectrometry, Fluorescence; D013682:Teichoic Acids / Q000737:chemistry; D013696:Temperature; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C492821:CD5L protein, human; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D051122:Scavenger Receptors, Class B; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid