Limits...
The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23.

Hermann P, Armant M, Brown E, Rubio M, Ishihara H, Ulrich D, Caspary RG, Lindberg FP, Armitage R, Maliszewski C, Delespesse G, Sarfati M - J. Cell Biol. (1999)

Bottom Line: Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding.Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant.We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire Allergie, Centre de recherch¿e Louis-Charles Simard, Pavillon Notre-Dame, Centre Hospitalier Université de Montréal (CHUM), Montreal, Quebec H2L 4M1, Canada.

ABSTRACT
The vitronectin receptor, alphavbeta3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-beta3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.

Show MeSH

Related in: MedlinePlus

sCD23 and Vn share the same functional receptor,  VnR/CD47 complex. (A) sCD23 binds to αv/CD51 and Vn to  αvβ3 (CD51/CD61) conformational site while neither bind to  CD47. Binding of Vn to αvβ3 (CD51/CD61) obliterates sCD23  binding site, and vice versa. (B and C) Anti-CD47 and anti-β3  (CD61) mAbs suppress Vn binding and function (left) while they  inhibit sCD23 function, but not binding (right).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2132927&req=5

Figure 9: sCD23 and Vn share the same functional receptor, VnR/CD47 complex. (A) sCD23 binds to αv/CD51 and Vn to αvβ3 (CD51/CD61) conformational site while neither bind to CD47. Binding of Vn to αvβ3 (CD51/CD61) obliterates sCD23 binding site, and vice versa. (B and C) Anti-CD47 and anti-β3 (CD61) mAbs suppress Vn binding and function (left) while they inhibit sCD23 function, but not binding (right).

Mentions: Our results can be summarized in the schematic model presented in Fig. 9. We first postulate (Fig. 9 A) that sCD23 and Vn have distinct recognition sites on the αvβ3/ CD47 complex. sCD23 binds to αv (CD51) and Vn to αvβ3 (CD51/CD61) conformational site. Binding of Vn may induce structural changes in the integrin complex leading to the masking of sCD23 binding sites, and vice versa. This hypothesis is based on observations that Vn, anti-αv mAb (clone AMF7), but not clone LM609 (which specifically recognizes Vn binding site), nor RGDS peptide inhibited sCD23 binding and function (Figs. 4 and 5), and sCD23 directly bound to αv chain (Figs. 6–8). However, CD47 was not a direct ligand for sCD23 while its coexpression improved sCD23 binding to αv/CD51. sCD23 bound CD47 deficient cell lines, but failed to bind CD47 in the absence of αv/CD51 integrin (THP-1 cell line, erythrocytes and recombinant CD47 protein; Fig. 8, and data not shown).


The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23.

Hermann P, Armant M, Brown E, Rubio M, Ishihara H, Ulrich D, Caspary RG, Lindberg FP, Armitage R, Maliszewski C, Delespesse G, Sarfati M - J. Cell Biol. (1999)

sCD23 and Vn share the same functional receptor,  VnR/CD47 complex. (A) sCD23 binds to αv/CD51 and Vn to  αvβ3 (CD51/CD61) conformational site while neither bind to  CD47. Binding of Vn to αvβ3 (CD51/CD61) obliterates sCD23  binding site, and vice versa. (B and C) Anti-CD47 and anti-β3  (CD61) mAbs suppress Vn binding and function (left) while they  inhibit sCD23 function, but not binding (right).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2132927&req=5

Figure 9: sCD23 and Vn share the same functional receptor, VnR/CD47 complex. (A) sCD23 binds to αv/CD51 and Vn to αvβ3 (CD51/CD61) conformational site while neither bind to CD47. Binding of Vn to αvβ3 (CD51/CD61) obliterates sCD23 binding site, and vice versa. (B and C) Anti-CD47 and anti-β3 (CD61) mAbs suppress Vn binding and function (left) while they inhibit sCD23 function, but not binding (right).
Mentions: Our results can be summarized in the schematic model presented in Fig. 9. We first postulate (Fig. 9 A) that sCD23 and Vn have distinct recognition sites on the αvβ3/ CD47 complex. sCD23 binds to αv (CD51) and Vn to αvβ3 (CD51/CD61) conformational site. Binding of Vn may induce structural changes in the integrin complex leading to the masking of sCD23 binding sites, and vice versa. This hypothesis is based on observations that Vn, anti-αv mAb (clone AMF7), but not clone LM609 (which specifically recognizes Vn binding site), nor RGDS peptide inhibited sCD23 binding and function (Figs. 4 and 5), and sCD23 directly bound to αv chain (Figs. 6–8). However, CD47 was not a direct ligand for sCD23 while its coexpression improved sCD23 binding to αv/CD51. sCD23 bound CD47 deficient cell lines, but failed to bind CD47 in the absence of αv/CD51 integrin (THP-1 cell line, erythrocytes and recombinant CD47 protein; Fig. 8, and data not shown).

Bottom Line: Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding.Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant.We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire Allergie, Centre de recherch¿e Louis-Charles Simard, Pavillon Notre-Dame, Centre Hospitalier Université de Montréal (CHUM), Montreal, Quebec H2L 4M1, Canada.

ABSTRACT
The vitronectin receptor, alphavbeta3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-beta3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.

Show MeSH
Related in: MedlinePlus