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

Anti-CD47 mAb inhibits CD23 costimulation of IFN-γ  production. (A) Dose-dependent inhibition of IFN-γ production  in IL-2 plus sCD23 stimulated coculture system by mAb clone  BRIC126 and F(ab′)2 fragments of mAb clone B6H12. One representative experiment out of two. (B) Anti-CD47 mAb (clone  B6H12) inhibition of IFN-γ secretion by T cells cocultured with  autologous monocytes and increasing numbers of untransfected  or CD23-transfected CHO cells. Similar data were obtained using clone 10G2 in three independent experiments. (C and D)  Anti-CD47 mAbs (clone B6H12) mediated inhibition of IFN-γ  and IL-12 secretion in cocultures of IL-2– or IL-15–stimulated T  cells and autologous monocytes in the absence or presence of  sCD23. Mean ± SD of six experiments. Anti-CD47 mAb inhibition in IL-2– or IL-15–stimulated cocultures, for IFN-γ production P < 0.001, and P < 0.01 for IL-12 secretion.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2132927&req=5

Figure 2: Anti-CD47 mAb inhibits CD23 costimulation of IFN-γ production. (A) Dose-dependent inhibition of IFN-γ production in IL-2 plus sCD23 stimulated coculture system by mAb clone BRIC126 and F(ab′)2 fragments of mAb clone B6H12. One representative experiment out of two. (B) Anti-CD47 mAb (clone B6H12) inhibition of IFN-γ secretion by T cells cocultured with autologous monocytes and increasing numbers of untransfected or CD23-transfected CHO cells. Similar data were obtained using clone 10G2 in three independent experiments. (C and D) Anti-CD47 mAbs (clone B6H12) mediated inhibition of IFN-γ and IL-12 secretion in cocultures of IL-2– or IL-15–stimulated T cells and autologous monocytes in the absence or presence of sCD23. Mean ± SD of six experiments. Anti-CD47 mAb inhibition in IL-2– or IL-15–stimulated cocultures, for IFN-γ production P < 0.001, and P < 0.01 for IL-12 secretion.

Mentions: We investigated the mechanisms underlying the suppression of IFN-γ production by anti-CD47 mAbs. In addition to 10G2 mAb of the IgM isotype, the F(ab)′2 fragments of B6H12 or intact BRIC126 mAb suppressed, in a dose-dependent manner, the ability of IL-2 and sCD23 to augment the production of IFN-γ by T cells cocultured with monocytes, demonstrating that the inhibition of IFN-γ secretion by anti-CD47 mAb was not Fc-mediated (Fig. 2 A). Interestingly, IFN-γ secretion by IL-2–stimulated T cells cocultured with monocytes and graded numbers of CD23-transfected CHO cells, was also abrogated by anti-CD47 mAbs (Fig. 2 B).


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)

Anti-CD47 mAb inhibits CD23 costimulation of IFN-γ  production. (A) Dose-dependent inhibition of IFN-γ production  in IL-2 plus sCD23 stimulated coculture system by mAb clone  BRIC126 and F(ab′)2 fragments of mAb clone B6H12. One representative experiment out of two. (B) Anti-CD47 mAb (clone  B6H12) inhibition of IFN-γ secretion by T cells cocultured with  autologous monocytes and increasing numbers of untransfected  or CD23-transfected CHO cells. Similar data were obtained using clone 10G2 in three independent experiments. (C and D)  Anti-CD47 mAbs (clone B6H12) mediated inhibition of IFN-γ  and IL-12 secretion in cocultures of IL-2– or IL-15–stimulated T  cells and autologous monocytes in the absence or presence of  sCD23. Mean ± SD of six experiments. Anti-CD47 mAb inhibition in IL-2– or IL-15–stimulated cocultures, for IFN-γ production P < 0.001, and P < 0.01 for IL-12 secretion.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Anti-CD47 mAb inhibits CD23 costimulation of IFN-γ production. (A) Dose-dependent inhibition of IFN-γ production in IL-2 plus sCD23 stimulated coculture system by mAb clone BRIC126 and F(ab′)2 fragments of mAb clone B6H12. One representative experiment out of two. (B) Anti-CD47 mAb (clone B6H12) inhibition of IFN-γ secretion by T cells cocultured with autologous monocytes and increasing numbers of untransfected or CD23-transfected CHO cells. Similar data were obtained using clone 10G2 in three independent experiments. (C and D) Anti-CD47 mAbs (clone B6H12) mediated inhibition of IFN-γ and IL-12 secretion in cocultures of IL-2– or IL-15–stimulated T cells and autologous monocytes in the absence or presence of sCD23. Mean ± SD of six experiments. Anti-CD47 mAb inhibition in IL-2– or IL-15–stimulated cocultures, for IFN-γ production P < 0.001, and P < 0.01 for IL-12 secretion.
Mentions: We investigated the mechanisms underlying the suppression of IFN-γ production by anti-CD47 mAbs. In addition to 10G2 mAb of the IgM isotype, the F(ab)′2 fragments of B6H12 or intact BRIC126 mAb suppressed, in a dose-dependent manner, the ability of IL-2 and sCD23 to augment the production of IFN-γ by T cells cocultured with monocytes, demonstrating that the inhibition of IFN-γ secretion by anti-CD47 mAb was not Fc-mediated (Fig. 2 A). Interestingly, IFN-γ secretion by IL-2–stimulated T cells cocultured with monocytes and graded numbers of CD23-transfected CHO cells, was also abrogated by anti-CD47 mAbs (Fig. 2 B).

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