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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.

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Related in: MedlinePlus

Suppression of sCD23-induced TNF-α release by anti-β3 (CD61) mAb and Vn. sCD23-activated monocytes were cultured with anti-β3 (CD61) clone AP3, anti-αvβ3 (CD51/CD61;  clone LM609), or isotype-matched mAbs (A) and with soluble  Vn or Fn (20 μg/ml, B). Mean ± SD of four experiments (P <  0.01).
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Figure 4: Suppression of sCD23-induced TNF-α release by anti-β3 (CD61) mAb and Vn. sCD23-activated monocytes were cultured with anti-β3 (CD61) clone AP3, anti-αvβ3 (CD51/CD61; clone LM609), or isotype-matched mAbs (A) and with soluble Vn or Fn (20 μg/ml, B). Mean ± SD of four experiments (P < 0.01).

Mentions: Several studies indicate that CD47 is physically and functionally associated with the vitronectin receptor, αvβ3. Both anti-CD47 and anti-β3 (CD61) mAbs can block binding of Vn, but not Fn, to αvβ3, even though Vn does not bind to CD47 (Brown et al., 1990; Lindberg et al., 1993). Therefore, we examined the biological effects of anti-β3 mAb and the natural ligands of VnR (Vn and Fn) on sCD23 function. It is important to note that all cultures were performed in HB101 serum-free medium to eliminate FCS as a source of Vn and Fn. The results (Fig. 4) suggested that Vn and sCD23 might share the same receptor, namely VnR/CD47 complex. Anti-β3 mAb suppressed sCD23 function, as defined by TNF-α secretion and IFN-γ production (Fig. 4 A, and data not shown). Furthermore, soluble Vn, but not Fn, suppressed sCD23-induced TNF-α release by purified monocytes (Fig. 4 B). sCD23 and Vn most likely bound to distinct epitopes on αvβ3, since an anti-αvβ3 mAb (clone LM609), which specifically inhibited Vn binding and function (Gao et al., 1996a), and RGDS peptide had no suppressive activity (Fig. 4 A, 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)

Suppression of sCD23-induced TNF-α release by anti-β3 (CD61) mAb and Vn. sCD23-activated monocytes were cultured with anti-β3 (CD61) clone AP3, anti-αvβ3 (CD51/CD61;  clone LM609), or isotype-matched mAbs (A) and with soluble  Vn or Fn (20 μg/ml, B). Mean ± SD of four experiments (P <  0.01).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Suppression of sCD23-induced TNF-α release by anti-β3 (CD61) mAb and Vn. sCD23-activated monocytes were cultured with anti-β3 (CD61) clone AP3, anti-αvβ3 (CD51/CD61; clone LM609), or isotype-matched mAbs (A) and with soluble Vn or Fn (20 μg/ml, B). Mean ± SD of four experiments (P < 0.01).
Mentions: Several studies indicate that CD47 is physically and functionally associated with the vitronectin receptor, αvβ3. Both anti-CD47 and anti-β3 (CD61) mAbs can block binding of Vn, but not Fn, to αvβ3, even though Vn does not bind to CD47 (Brown et al., 1990; Lindberg et al., 1993). Therefore, we examined the biological effects of anti-β3 mAb and the natural ligands of VnR (Vn and Fn) on sCD23 function. It is important to note that all cultures were performed in HB101 serum-free medium to eliminate FCS as a source of Vn and Fn. The results (Fig. 4) suggested that Vn and sCD23 might share the same receptor, namely VnR/CD47 complex. Anti-β3 mAb suppressed sCD23 function, as defined by TNF-α secretion and IFN-γ production (Fig. 4 A, and data not shown). Furthermore, soluble Vn, but not Fn, suppressed sCD23-induced TNF-α release by purified monocytes (Fig. 4 B). sCD23 and Vn most likely bound to distinct epitopes on αvβ3, since an anti-αvβ3 mAb (clone LM609), which specifically inhibited Vn binding and function (Gao et al., 1996a), and RGDS peptide had no suppressive activity (Fig. 4 A, 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