Factors secreted by untreated psoriatic monocytes enhance neutrophil functions

Paolo Daniele Pigatto, Laura Bersani Pigatto, Andrea Bigardi, Gianfranco Altomare, Aldo Fabrizio Finzi

Research output: Contribution to journalArticle

Abstract

Monocytes stimulated with bacterial lipopolysaccharides (LPS) release mediators that induce increased responses of human granulocytes. Recently we showed that psoriatic monocytes can stimulate neutrophil chemotaxis, phagocytosis, and O2 - production without addition of LPS and this effect is inhibited by cyclosporin A. We have now investigated the presence of cytokines in supernatants from cultures of psoriatic monocytes (resting monocytes). These cells were cultured for 24 h in endotoxin-free medium. Normal human neutrophils were then incubated for 1 h with the resulting supernatants (sMS, or conditioned media). The sMS from unstimulated psoriatic monocytes significantly enhanced neutrophil chemotaxis and superoxide anion production. The enhancing factors are protein in nature and require on going protein synthesis, demonstrated by the facts that the activity in conditioned medium is labile to heat denaturation at 100°C for 10 min, is not produced by monocytes cultured in the presence of puromycin, and is proteinase sensitive. Additional evidence suggested that extremes of pH inhibit activity. None of the conditioned media treated in these ways activated neutrophils. The neutrophil function-enhancing factors derived from psoriatic monocytes are in part cytokines, including TNF and GM-CSF. The support for this conclusion is the higher level of TNF and GM-CSF in media conditioned by psoriatic monocytes than in media conditioned by normal human monocytes, the inhibition of TNF production and neutrophil stimulating activity by cyclo-sporin A, and the inhibition of neutrophil stimulating activity in conditioned media preincubated with anti-TNF and anti-GM-CSF antibodies. It is concluded that psoriatic monocytes spontaneously produce higher than normal levels of TNFα, GM-CSF, and, perhaps, other cytokines that might be responsible for the enhanced activity of psoriatic neutrophils.

Original languageEnglish
Pages (from-to)372-376
Number of pages5
JournalJournal of Investigative Dermatology
Volume94
Issue number3
Publication statusPublished - Mar 1990

    Fingerprint

ASJC Scopus subject areas

  • Dermatology

Cite this

Pigatto, P. D., Pigatto, L. B., Bigardi, A., Altomare, G., & Finzi, A. F. (1990). Factors secreted by untreated psoriatic monocytes enhance neutrophil functions. Journal of Investigative Dermatology, 94(3), 372-376.