Streptococcal inhibitor of complement inhibits two additional components of the mucosal innate immune system: Secretory leukocyte proteinase inhibitor and lysozyme

被引:75
作者
Fernie-King, BA [1 ]
Seilly, DJ [1 ]
Davies, A [1 ]
Lachmann, PJ [1 ]
机构
[1] Univ Cambridge, Ctr Vet Sci, Microbial Immunol Unit, Cambridge CB3 0ES, England
关键词
D O I
10.1128/IAI.70.9.4908-4916.2002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Streptococcal inhibitor of complement (SIC) is a 31-kDa extracellular protein of a few, very virulent, strains of Streptococcus pyogenes (particularly M1 strains). It is secreted in large quantities (about 5 mg/liter) and inhibits complement lysis by blocking the membrane insertion site on C5b67. We describe investigations into the interaction of SIC with three further major components of the innate immune system found in airway surface liquid, namely, secretory leukocyte proteinase inhibitor (SLPI), lysozyme, and lactoferrin. Enzyme-linked immunosorbent assays showed that SIC binds to SLPI and to both human and hen egg lysozyme (HEL) but not to lactoferrin. Studies using I-125-labeled proteins showed that SIC binds approximately two molecules of SLPI and four molecules of lysozyme. SLPI binding shows little temperature dependence and a small positive enthalpy, suggesting that the binding is largely hydrophobic. By contrast, lysozyme binding shows strong temperature dependence and a substantial negative enthalpy, suggesting that the binding is largely ionic. Lysozyme is precipitated from solution by SIC. Further studies examined the ability of SIC to block the biological activities of SLPI and lysozyme. An M1 strain of group A streptococci was killed by SLPI, and the antibacterial activity of this protein was inhibited by SIC. SIC did not inhibit the antiproteinase activity of SLPI, implying that there is specific inhibition of the antibacterial domain. The antibacterial and enzymatic activities of lysozyme were also inhibited by SIC. SIC is the first biological inhibitor of the antibacterial action of SLPI to be described and may prove to be an important tool for investigating this activity in vivo. Inhibition of the antibacterial actions of SLPI and lysozyme would be advantageous to S. pyogenes in establishing colonization on mucosal surfaces, and we propose that this is the principal function of SIC.
引用
收藏
页码:4908 / 4916
页数:9
相关论文
共 31 条
[21]   SECRETORY LEUKOCYTE PROTEASE INHIBITOR - A HUMAN SALIVA PROTEIN EXHIBITING ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS-1 ACTIVITY IN-VITRO [J].
MCNEELY, TB ;
DEALY, M ;
DRIPPS, DJ ;
ORENSTEIN, JM ;
EISENBERG, SP ;
WAHL, SM .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (01) :456-464
[22]   ADAPTIVE EVOLUTION OF HIGHLY MUTABLE LOCI IN PATHOGENIC BACTERIA [J].
MOXON, ER ;
RAINEY, PB ;
NOWAK, MA ;
LENSKI, RE .
CURRENT BIOLOGY, 1994, 4 (01) :24-33
[23]   THE ACID-STABLE PROTEINASE-INHIBITOR OF HUMAN MUCOUS SECRETIONS (HUSI-I, ANTILEUKOPROTEASE) - COMPLETE AMINO-ACID-SEQUENCE AS REVEALED BY PROTEIN AND CDNA SEQUENCING AND STRUCTURAL HOMOLOGY TO WHEY PROTEINS AND RED-SEA TURTLE PROTEINASE-INHIBITOR [J].
SEEMULLER, U ;
ARNHOLD, M ;
FRITZ, H ;
WIEDENMANN, K ;
MACHLEIDT, W ;
HEINZEL, R ;
APPELHANS, H ;
GASSEN, HG ;
LOTTSPEICH, F .
FEBS LETTERS, 1986, 199 (01) :43-48
[24]   Elafin (elastase-specific inhibitor) has anti-microbial activity against Gram-positive and Gram-negative respiratory pathogens [J].
Simpson, AJ ;
Maxwell, AI ;
Govan, JRW ;
Haslett, C ;
Sallenave, JM .
FEBS LETTERS, 1999, 452 (03) :309-313
[25]   Synergistic and additive killing by antimicrobial factors found in human airway surface liquid [J].
Singh, PK ;
Tack, BF ;
McCray, PB ;
Welsh, MJ .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2000, 279 (05) :L799-L805
[26]   Remarkable attachment of lactoferrin to Streptococcus pyogenes during acute pharyngotonsillitis [J].
Stenfors, LE ;
Bye, HM ;
Vorland, LH .
ACTA OTO-LARYNGOLOGICA, 2001, 121 (05) :637-642
[27]   Antileukoprotease: An endogenous protein in the innate mucosal defense against fungi [J].
Tomee, JFC ;
Hiemstra, PS ;
HeinzelWieland, R ;
Kauffman, HF .
JOURNAL OF INFECTIOUS DISEASES, 1997, 176 (03) :740-747
[28]   Antimicrobial peptides and proteins in the innate defense of the airway surface [J].
Travis, SM ;
Singh, PK ;
Welsh, MJ .
CURRENT OPINION IN IMMUNOLOGY, 2001, 13 (01) :89-95
[29]   Identification of a novel secretory leukocyte protease inhibitor-binding protein involved in membrane phospholipid movement [J].
Tseng, CC ;
Tseng, CP .
FEBS LETTERS, 2000, 475 (03) :232-236
[30]   Antileukoprotease in human skin: An antibiotic peptide constitutively produced by keratinocytes [J].
Wiedow, O ;
Harder, J ;
Bartels, J ;
Streit, V ;
Christophers, E .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 248 (03) :904-909