Mannose binding lectin and lung collectins interact with Toll-like receptor 4 and MD-2 by different mechanisms

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• 作者：Takeyuki Shimizu ; Chiaki Nishitani ; Hiroaki Mitsuzawa ; Shigeru Ariki ; Motoko Takahashi ; Katsuki Ohtani ; Nobutaka Wakamiya ; Yoshio Kuroki
• 关键词：Collectin ; Mannose binding lectin ; Surfactant protein ; Toll-like receptor 4 ; MD-2 ; Innate immunity
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：1790
• 期：12
• 页码：1705-1710
• 全文大小：512 K

文摘

Background

We have previously shown that lung collectins, surfactant protein A (SP-A) and surfactant protein D, interact with Toll-like receptor (TLR) 2, TLR4, or MD-2. Bindings of lung collectins to TLR2 and TLR4/MD-2 result in the alterations of signaling through these receptors, suggesting the immunomodulatory functions of lung collectins. Mannose binding lectin (MBL) is another collectin molecule which has structural homology to SP-A. The interaction between MBL and TLRs has not yet been determined.

Methods

We prepared recombinant MBL, and analyzed its bindings to recombinant soluble forms of TLR4 (sTLR4) and MD-2.

Results

MBL bound to sTLR4 and MD-2. The interactions were Ca²⁺-dependent and inhibited by mannose or monoclonal antibody against the carbohydrate-recognition domain of MBL. Treatment of sTLR4 or MD-2 by peptide N-glycosidase F significantly decreased the binding of MBL. SP-A bound to deglycosylated sTLR4, and this property did not change in chimeric molecules of SP-A/MBL in which Glu¹⁹⁵–Phe²²⁸ or Thr¹⁷⁴–Gly¹⁹⁴ of SP-A were replaced with the corresponding MBL sequences.

General Significance

These results suggested that MBL binds to TLR4 and MD-2 through the carbohydrate-recognition domain, and that oligosaccharide moieties of TLR4 and MD-2 are important for recognition by MBL. Since our previous studies indicated that lung collectins bind to the peptide portions of TLRs, MBL and lung collectins interact with TLRs by different mechanisms. These direct interactions between MBL and TLR4 or MD-2 suggest that MBL may modulate cellular responses by altering signals through TLRs.