Pattern Recognition Scavenger Receptors, SR-A and CD36, Have an Additive Role in the Development of Colitis in Mice

  • Helieh S. Oz
  • Jian Zhong
  • Willem J. S. de Villiers
Original Article


The multifunctional pattern recognition scavenger receptors, SR-A and CD36, are predominantly expressed by lamina propria macrophages and considered important in innate immunity. We examined the role of these receptors in the pathophysiology of inflammatory bowel disease. Colitis was induced in wild type (WT), SR-A−/−, CD36−/−, and SR-A/CD36 double deficient mice by administering DSS. DSS-induced moderately severe colitis in WT mice was manifested by weight loss, reduced hematocrit, and pathology. SR-A/CD36 double deficient mice developed significantly more severe colitis as indicated by anemia (P < 0.01), decreased colonic length due to inflammation (P < 0.01), and lesions when compared with WT and single deficient animals. Serum amyloid A was significantly more elevated in SR-A/CD36−/− mice (P < 0.01) compared with WT and single deficient animals. However, the spleens of WT mice (P < 0.05) were significantly enlarged. Inflammatory cytokine levels were considerably increased in WT mice (IL-6 P < 0.001, TNFα P < 0.01). In contrast, SR-A deficient mice maintained more normal body and splenic weight and developed less severe colonic lesions compared to other groups. In conclusion, our data indicate that SR-A/CD36 double deficiency leads to more severe colonic lesions and dysregulated inflammatory response as compared with single SR-A or CD36 deficiency in colitis, suggesting additive effects between these two receptors in this model.


Scavenger receptors Macrophages SR-A CD36 Colitis 



Dextran sodium sulphate


Interferon gamma




Low-density lipoprotein




Lipoteichoic acid



Scavenger receptor A


Tumor necrosis factor





This study was partially supported by the National Institutes of Health grant NCCAM-AT1490 and NCRR P20RR020145,COHR-Pilot Project (H. S. Oz).


  1. 1.
    Gordon S. The macrophage scavenger receptor type A is expressed by activated macrophages and protects the host against lethal endotoxic shock. J Exp Med. 1997;186:1431–1439. doi: 10.1084/jem.186.9.1431.CrossRefPubMedGoogle Scholar
  2. 2.
    Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002;111:927–930. doi: 10.1016/S0092-8674(02)01201-1.CrossRefPubMedGoogle Scholar
  3. 3.
    Platt N, Gordon S. Is the class A macrophage scavenger receptor (SR-A) multifunctional?—The mouse’s tale. J Clin Invest. 2001;108:649–654.PubMedGoogle Scholar
  4. 4.
    Geng YJ, Hansson GK. Interferon-gamma inhibits scavenger receptor expression and foam cell formation in human monocyte-derived macrophages. J Clin Invest. 1992;89:1322–1330. doi: 10.1172/JCI115718.CrossRefPubMedGoogle Scholar
  5. 5.
    Hsu HY, Nicholson AC, Hajjar DP. Inhibition of macrophage scavenger receptor activity by tumor necrosis factor-alpha is transcriptionally and post-transcriptionally regulated. J Biol Chem. 1996;271:7767–7773. doi: 10.1074/jbc.271.13.7767.CrossRefPubMedGoogle Scholar
  6. 6.
    De Villiers WJS, Fraser IP, Hughes DA, Doyle AG, Gordon S. Macrophage-colony-stimulating factor selectively enhances macrophage scavenger receptor expression and function. J Exp Med. 1994;180:705–709. doi: 10.1084/jem.180.2.705.CrossRefPubMedGoogle Scholar
  7. 7.
    De Villiers WJS, Fraser IP, Gordon S. Cytokine and growth factor regulation of macrophage scavenger receptor expression and function. Immunol Lett. 1994;43:73–79. doi: 10.1016/0165-2478(94)00148-0.CrossRefPubMedGoogle Scholar
  8. 8.
    Guidez F, Li AC, Horvai A, Welch JS, Glass CK. Differential utilization of Ras signaling pathways by macrophage colony-stimulating factor (CSF) and granulocyte-macrophage CSF receptors during macrophage differentiation. Mol Cell Biol. 1998;18:3851–3861.PubMedGoogle Scholar
  9. 9.
    Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature. 1998;391:79–82. doi: 10.1038/34178.CrossRefPubMedGoogle Scholar
  10. 10.
    Febbraio M, Hajjar DP, Silverstein RL. CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest. 2001;108:785–791.PubMedGoogle Scholar
  11. 11.
    Ockenhouse CF, Chulay JD. Plasmodium falciparum sequestration: OKM5 antigen (CD36) mediates cytoadherence of parasitized erythrocytes to a myelomonocytic cell line. J Infect Dis. 1988;157:584–588.PubMedGoogle Scholar
  12. 12.
    Oquendo P, Hundt E, Lawler J, Seed B. CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Cell. 1989;58:95–101. doi: 10.1016/0092-8674(89)90406-6.CrossRefPubMedGoogle Scholar
  13. 13.
    Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA. CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem. 1993;268:11811–11816.PubMedGoogle Scholar
  14. 14.
    Moore KJ, El Khoury J, Medeiros LA, et al. CD36-initiated signaling cascade mediates inflammatory effects of beta-amyloid. J Biol Chem. 2002;277:47373–47379. doi: 10.1074/jbc.M208788200.CrossRefPubMedGoogle Scholar
  15. 15.
    Medeiros LA, Khan T, El Khoury JB, et al. Fibrillar amyloid protein present in atheroma activates CD36 signal transduction. J Biol Chem. 2004;279:10643–10648. doi: 10.1074/jbc.M311735200.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhong J, Eckhart E, Oz HS, Bruemmer D, de Villiers W. Osteopontin deficiency protects mice from DSS-induced colitis. Inflamm Bowel Dis. 2006;12:790–796. doi: 10.1097/00054725-200608000-00015.CrossRefPubMedGoogle Scholar
  17. 17.
    Van Lenten BJ, Fogelman AM. Lipopolysaccharide-induced inhibition of scavenger receptor expression in human monocyte–macrophages is mediated through tumor necrosis factor-alpha. J Immunol. 1992;148:112–116.PubMedGoogle Scholar
  18. 18.
    Areschoug T, Waldemarsson J, Gordon S. Evasion of macrophage scavenger receptor A-mediated recognition by pathogenic streptococci. Eur J Immunol. 2008;38:3068–3079.CrossRefPubMedGoogle Scholar
  19. 19.
    Suzuki H, Kurihara Y, Takeya M, Kamada N, Kodama T, et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997;386:292–296. doi: 10.1038/386292a0.CrossRefPubMedGoogle Scholar
  20. 20.
    Thomas CA, Li Y, Kodama T, Suzuki H, Silverstein SC, El Khoury J. Protection from lethal gram-positive infection by macrophage scavenger receptor-dependent phagocytosis. J Exp Med. 2000;191:147–156.CrossRefPubMedGoogle Scholar
  21. 21.
    Haworth R, Platt N, Keshav S, et al. The macrophage scavenger receptor type A is expressed by activated macrophages and protects the host against lethal endotoxic shock. J Exp Med. 1997;186:1431–1439.CrossRefPubMedGoogle Scholar
  22. 22.
    Kobayashi Y, Miyaji C, Watanabe H, et al. Role of macrophage scavenger receptor in endotoxin shock. J Pathol. 2000;192:263–272.CrossRefPubMedGoogle Scholar
  23. 23.
    Hagiwara S, Takeya M, Suzuki H, et al. Role of macrophage scavenger receptors in hepatic granuloma formation in mice. Am J Pathol. 1999;154:705–720.PubMedGoogle Scholar
  24. 24.
    Singh U, Devaraj S, Jialal I. Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr. 2005;25:151–174.CrossRefPubMedGoogle Scholar
  25. 25.
    Takeda N, Manabe I, Shindo T, et al. Synthetic retinoid Am80 reduces scavenger receptor expression and atherosclerosis in mice by inhibiting IL-6. Arterioscler Thromb Vasc Biol. 2006;26:1177–1183.CrossRefPubMedGoogle Scholar
  26. 26.
    Mytar B, Woloszyn M, Macura-Biegun A, et al. Involvement of pattern recognition receptors in the induction of cytokines and reactive oxygen intermediates production by human monocytes/macrophages stimulated with tumour cells. Anticancer Res. 2004;24:2287–2293.PubMedGoogle Scholar
  27. 27.
    Li WX, Howard RJ, Leung LL. Identification of SVTCG in thrombospondin as the conformation-dependent, high affinity binding site for its receptor, CD36. J Biol Chem. 1993;268:16179–16184.PubMedGoogle Scholar
  28. 28.
    Fadok VA, Warner ML, Bratton DL, Henson PM. CD36 is required for phagocytosis of apoptotic cells by human macrophages that use either a phosphatidylserine receptor or the vitronectin receptor (alpha vs. beta 3). J Immunol. 1998;161:6250–6257.PubMedGoogle Scholar
  29. 29.
    Stolzing A, Grune T. Neuronal apoptotic bodies: phagocytosis and degradation by primary microglial cells. FASEB J. 2004;18:743–745.PubMedGoogle Scholar
  30. 30.
    Ren Y, Silverstein RL, Allen J, Savill J. CD36 gene transfer confers capacity for phagocytosis of cells undergoing apoptosis. J Exp Med. 1995;181:1857–1862.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Helieh S. Oz
    • 1
    • 2
  • Jian Zhong
    • 2
    • 3
  • Willem J. S. de Villiers
    • 2
    • 3
  1. 1.Center for Oral Health Research, College of DentistryUniversity of Kentucky Medical CenterLexingtonUSA
  2. 2.Department of Internal MedicineUniversity of Kentucky Medical CenterLexingtonUSA
  3. 3.Division of Digestive DiseasesUniversity of Kentucky Medical CenterLexingtonUSA

Personalised recommendations