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 inhibition of sCD23-induced monokine release by purified monocytes. Monocytes (106/ml) were cultured in the absence or presence of sCD23 or LPS with or without  anti-CD47 mAb (clone 10G2). After overnight cultures, TNF-α  (A), IL-1β, IL-8, or PGE2 (B) was measured in the culture supernatant. Mean ± SD of six experiments (*P < 0.05, **P < 0.01).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2132927&req=5

Figure 3: Anti-CD47 mAb inhibition of sCD23-induced monokine release by purified monocytes. Monocytes (106/ml) were cultured in the absence or presence of sCD23 or LPS with or without anti-CD47 mAb (clone 10G2). After overnight cultures, TNF-α (A), IL-1β, IL-8, or PGE2 (B) was measured in the culture supernatant. Mean ± SD of six experiments (*P < 0.05, **P < 0.01).

Mentions: Because sCD23 directly triggers TNF-α release by purified monocytes (Armant et al., 1995), and monocytes express CD47 (Table I), we examined the effect anti-CD47 mAb had on sCD23-induced monokine release by monocytes. Anti-CD47 mAb significantly suppressed the induction by sCD23 of TNF-α, IL-1β, and PGE2 without affecting IL-8 secretion (Fig. 3). The data (i.e., inhibition of TNF-α and IL-12 production) provide a mechanism by which anti-CD47 mAb can suppress sCD23 costimulation of IFN-γ production.


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 inhibition of sCD23-induced monokine release by purified monocytes. Monocytes (106/ml) were cultured in the absence or presence of sCD23 or LPS with or without  anti-CD47 mAb (clone 10G2). After overnight cultures, TNF-α  (A), IL-1β, IL-8, or PGE2 (B) was measured in the culture supernatant. Mean ± SD of six experiments (*P < 0.05, **P < 0.01).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Anti-CD47 mAb inhibition of sCD23-induced monokine release by purified monocytes. Monocytes (106/ml) were cultured in the absence or presence of sCD23 or LPS with or without anti-CD47 mAb (clone 10G2). After overnight cultures, TNF-α (A), IL-1β, IL-8, or PGE2 (B) was measured in the culture supernatant. Mean ± SD of six experiments (*P < 0.05, **P < 0.01).
Mentions: Because sCD23 directly triggers TNF-α release by purified monocytes (Armant et al., 1995), and monocytes express CD47 (Table I), we examined the effect anti-CD47 mAb had on sCD23-induced monokine release by monocytes. Anti-CD47 mAb significantly suppressed the induction by sCD23 of TNF-α, IL-1β, and PGE2 without affecting IL-8 secretion (Fig. 3). The data (i.e., inhibition of TNF-α and IL-12 production) provide a mechanism by which anti-CD47 mAb can suppress sCD23 costimulation of IFN-γ production.

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