Structure of the Human Macrophage MARCO Receptor and Characterization of Its Bacteria-binding Region

Elomaa, Outi; Sankala, Marko; Pikkarainen, Timo; Bergmann, Ulrich; Tuuttila, Ari; Raatikainen-Ahokas, Anne; Sariola, Hannu; Tryggvason, Karl

doi:10.1074/jbc.273.8.4530

Cited by 132 publications

(128 citation statements)

References 26 publications

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“…These properties are in line with those displayed by other members of the SRCR superfamily such as MARCO, 40 SAG/DMBT-1, 9,41 sCD6 11 and sCD163, 42 and reinforces the notion that the PRR function could be one unifying trait shared by this superfamily's members. AIM/Api6/ CD5L has also shown other immunomodulating properties such as the ability to impair PAMP-induced pro-inflammatory cytokine production, which could be useful in protecting tissues from local inflammation damage, and also from more generalized effects of PAMPs such as sepsis and septic shock syndrome.…”

Section: Discussionsupporting

confidence: 68%

The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression

et al. 2014

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Apoptosis inhibitor of macrophages (AIMs), a homologue of human Spa, is a mouse soluble member of the scavenger receptor cysteine-rich superfamily (SRCR-SF). This family integrates a group of proteins expressed by innate and adaptive immune cells for which no unifying function has yet been described. Pleiotropic functions have been ascribed to AIM, from viability support in lymphocytes during thymic selection to lipid metabolism and anti-inflammatory effects in autoimmune pathologies. In the present report, the pathogen binding properties of AIM have been explored. By using a recombinant form of AIM (rAIM) expressed in mammalian cells, it is shown that this protein is able to bind and aggregate Gram-positive and Gram-negative bacteria, as well as pathogenic and saprophytic fungal species. Importantly, endogenous AIM from mouse serum also binds to microorganisms and secretion of AIM was rapidly induced in mouse spleen macrophages following exposure to conserved microbial cell wall components. Cytokine release induced by well-known bacterial and fungal Toll-like receptor (TLR) ligands on mouse splenocytes was also inhibited in the presence of rAIM. Furthermore, mouse models of pathogen-associated molecular patterns (PAMPs)-induced septic shock of bacterial and fungal origin showed that serum AIM levels changed in a time-dependent manner. Altogether, these data suggest that AIM plays a general homeostatic role by supporting innate humoral defense during pathogen aggression.

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Section: Discussionsupporting

confidence: 68%

The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression

et al. 2014

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“…A study on the bacteria binding of the human macrophage MARCO receptor (38), another member of the SRCR superfamily, has demonstrated that a peptide encompassing residues 431-441 (RGRAEVYYSGT) was responsible for binding of MARCO to S. aureus and E. coli (39). This region corresponds to residues 1-11 of SRCRP2 with 55% homology.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Bacteria-binding Peptide Domain on Salivary Agglutinin (gp-340/DMBT1), a Member of the Scavenger Receptor Cysteine-rich Superfamily

Bikker¹,

Ligtenberg²,

Nazmi³

et al. 2002

Journal of Biological Chemistry

146

183

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Salivary agglutinin is encoded by DMBT1 and identical to gp-340, a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Salivary agglutinin/ DMBT1 is known for its Streptococcus mutans agglutinating properties. This 300 -400 kDa glycoprotein is composed of conserved peptide motifs: 14 SRCR domains that are separated by SRCR-interspersed domains (SIDs), 2 CUB (C1r/C1s Uegf Bmp1) domains, and a zona pellucida domain. We have searched for the peptide domains of agglutinin/DMBT1 responsible for bacteria binding. Digestion with endoproteinase Lys-C resulted in a protein fragment containing exclusively SRCR and SID domains that binds to S. mutans. To define more closely the S. mutans-binding domain, consensus-based peptides of the SRCR domains and SIDs were designed and synthesized. Only one of the SRCR peptides, designated SRCRP2, and none of the SID peptides bound to S. mutans. Strikingly, this peptide was also able to induce agglutination of S. mutans and a number of other bacteria. The repeated presence of this peptide in the native molecule endows agglutinin/DMBT1 with a general bacterial binding feature with a multivalent character. Moreover, our studies demonstrate for the first time that the polymorphic SRCR domains of salivary agglutinin/DMBT1 mediate ligand interactions.

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“…The Macrophage Receptor MARCO-MARCO also belongs to the class A scavenger receptors (53). In addition to one large 270-residue collagenous region, the extracellular C terminus of MARCO contains an SRCR domain involved in binding of Grampositive and -negative bacteria (10).…”

Section: Other Collagenous Transmembrane Proteins Andmentioning

confidence: 99%

Collagenous Transmembrane Proteins: Recent Insights into Biology and Pathology*

Franzke

Brückner

Bruckner‐Tuderman

2005

Journal of Biological Chemistry

150

138

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Structure of the Human Macrophage MARCO Receptor and Characterization of Its Bacteria-binding Region

Abstract: The primary structure of human macrophage receptor with collagenous structure (MARCO) was determined from cDNA clones and shown to be highly similar to that of mouse (Elomaa, O., Kangas, M., Sahlberg, C., Tuukkanen, J., Sormunen, R., Liakka, A., Thesleff, I., Kraal, G., and Tryggvason, K.

Cited by 132 publications

References 26 publications

The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression

The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression

Identification of the Bacteria-binding Peptide Domain on Salivary Agglutinin (gp-340/DMBT1), a Member of the Scavenger Receptor Cysteine-rich Superfamily

Collagenous Transmembrane Proteins: Recent Insights into Biology and Pathology*

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