Fibroblast stimulation in schistosomiasis. IV. Isolated egg granulomas elaborate a fibroblast chemoattractant in vitro

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Abstract

Hepatic fibrosis complicates the chronic granulomatous inflammatory reaction to Schistosoma mansoni eggs, and is the major cause of morbidity and mortality in human schistosomiasis. We previously presented evidence that schistosomal egg granulomas secreted factors that can stimulate fibroblast proliferation and collagen synthesis in vitro. We now report that serum-free supernatants from cultures of hepatic egg granulomas isolated from S. mansoni-infected mice contained activity that stimulated the directional migration of human and guinea pig dermal fibroblasts in modified Boyden chambers. This fibroblast chemotactic activity was also detected in culture supernatants of granuloma adherent cells highly enriched for macrophages (95% latex-ingesting) but not in culture supernatants from resident peritoneal macrophages of uninfected or infected mice. This suggests that granuloma macrophages are a source of the chemotactic activity. The chemoattractant had the properties of large molecular weight (>200,000 daltons; Sephadex G-200 gel filtration), pI ~4.5 (preparative flatbed isoelectrofocusing in granular matrix), heat stability (56°C; 45 min), and trypsin sensitivity. Since preincubation of the partially purified granuloma and adherent-cell derived chemoatractants with rabbit anti-human fibronectin antibody abolished their chemoatactic activity, it appears that the factor is antigenically similar to fibronectin. We propose that egg granuloma macrophages are activated in vivo to secrete a fibronectin-like molecule with activity that stimulates the directional migration of fibroblasts. This factor may therefore play a role in the local recruitment of fibroblasts and, in concert with other granuloma-derived factors, may play an important role in the pathogenesis of hepatic fibrosis in schistosomiasis.

Original languageEnglish (US)
Pages (from-to)1371-1375
Number of pages5
JournalJournal of Immunology
Volume130
Issue number3
StatePublished - 1983
Externally publishedYes

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Schistosomiasis
Chemotactic Factors
Granuloma
Ovum
Fibroblasts
Fibronectins
Schistosoma mansoni
Macrophages
Liver
Fibrosis
Latex
Peritoneal Macrophages
In Vitro Techniques
Trypsin
Eggs
Gel Chromatography
Guinea Pigs
Collagen
Hot Temperature
Molecular Weight

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Fibroblast stimulation in schistosomiasis. IV. Isolated egg granulomas elaborate a fibroblast chemoattractant in vitro. / Wyler, D. J.; Postlethwaite, Arnold.

In: Journal of Immunology, Vol. 130, No. 3, 1983, p. 1371-1375.

Research output: Contribution to journalArticle

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abstract = "Hepatic fibrosis complicates the chronic granulomatous inflammatory reaction to Schistosoma mansoni eggs, and is the major cause of morbidity and mortality in human schistosomiasis. We previously presented evidence that schistosomal egg granulomas secreted factors that can stimulate fibroblast proliferation and collagen synthesis in vitro. We now report that serum-free supernatants from cultures of hepatic egg granulomas isolated from S. mansoni-infected mice contained activity that stimulated the directional migration of human and guinea pig dermal fibroblasts in modified Boyden chambers. This fibroblast chemotactic activity was also detected in culture supernatants of granuloma adherent cells highly enriched for macrophages (95{\%} latex-ingesting) but not in culture supernatants from resident peritoneal macrophages of uninfected or infected mice. This suggests that granuloma macrophages are a source of the chemotactic activity. The chemoattractant had the properties of large molecular weight (>200,000 daltons; Sephadex G-200 gel filtration), pI ~4.5 (preparative flatbed isoelectrofocusing in granular matrix), heat stability (56°C; 45 min), and trypsin sensitivity. Since preincubation of the partially purified granuloma and adherent-cell derived chemoatractants with rabbit anti-human fibronectin antibody abolished their chemoatactic activity, it appears that the factor is antigenically similar to fibronectin. We propose that egg granuloma macrophages are activated in vivo to secrete a fibronectin-like molecule with activity that stimulates the directional migration of fibroblasts. This factor may therefore play a role in the local recruitment of fibroblasts and, in concert with other granuloma-derived factors, may play an important role in the pathogenesis of hepatic fibrosis in schistosomiasis.",
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N2 - Hepatic fibrosis complicates the chronic granulomatous inflammatory reaction to Schistosoma mansoni eggs, and is the major cause of morbidity and mortality in human schistosomiasis. We previously presented evidence that schistosomal egg granulomas secreted factors that can stimulate fibroblast proliferation and collagen synthesis in vitro. We now report that serum-free supernatants from cultures of hepatic egg granulomas isolated from S. mansoni-infected mice contained activity that stimulated the directional migration of human and guinea pig dermal fibroblasts in modified Boyden chambers. This fibroblast chemotactic activity was also detected in culture supernatants of granuloma adherent cells highly enriched for macrophages (95% latex-ingesting) but not in culture supernatants from resident peritoneal macrophages of uninfected or infected mice. This suggests that granuloma macrophages are a source of the chemotactic activity. The chemoattractant had the properties of large molecular weight (>200,000 daltons; Sephadex G-200 gel filtration), pI ~4.5 (preparative flatbed isoelectrofocusing in granular matrix), heat stability (56°C; 45 min), and trypsin sensitivity. Since preincubation of the partially purified granuloma and adherent-cell derived chemoatractants with rabbit anti-human fibronectin antibody abolished their chemoatactic activity, it appears that the factor is antigenically similar to fibronectin. We propose that egg granuloma macrophages are activated in vivo to secrete a fibronectin-like molecule with activity that stimulates the directional migration of fibroblasts. This factor may therefore play a role in the local recruitment of fibroblasts and, in concert with other granuloma-derived factors, may play an important role in the pathogenesis of hepatic fibrosis in schistosomiasis.

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