Cytokine release by macrophages after interacting with CSF-1 and extracellular matrix proteins: Characteristics of a mouse model of inflammatory responses in vitro

Sergey G. Kremlev, Andrei I. Chapoval, Robert Evans

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Extracellular matrix (ECM) proteins play a key role at sites of inflammation where they regulate the inflammatory properties of infiltrating leukocytes. Previous data indicated that the macrophage colony-stimulating factor (CSF-1 or M-CSF) primed subpopulations of mononuclear phagocytes (MNP) for differential inflammatory responses and rendered defined populations extremely sensitive to secondary stimulation as measured by cytokine gene expression. In this report, we focus on the question whether CSF-1 modified the inflammatory responsiveness of elicited peritoneal macrophages (PMφ), as a defined subpopulation of MNP, to secondary stimulation by ECM proteins as a component of inflammatory lesions. It was seen that CSF-1-primed PMφ responded to fibronectin (FN) and collagen type IV (COL IV) in vitro by releasing large amounts of IL-6 but released only minimal quantities when exposed to vitronectin (VN) or to untreated plastic surfaces. TNF-α and GM- CSF proteins were not released. Preincubation of the PMφ with CSF-1 or 10% FBS for up to 12 h prior to exposure to ECM proteins was shown to further enhance the release of IL-6 when the cells were cultured with FN but to result in a loss of secretory activity when placed on COL IV. In addition, preincubated PMφ in contact with FN were shown to release TNF-α but not GM- CSF. CSF-1 did not enhance VLA 4 (α4β1 or CD49d) but enhanced VLA 5 (α5β or CD49e) expression. However, blocking with either anti-VLA 4 or VLA 5 monoclonal antibodies inhibited the IL-6 response. These data suggest that CSF-1 primes elicited PMφ for differential expression of adhesion molecules that are required for binding to individual ECM proteins and for modulating inflammatory responses of MNP.

Original languageEnglish (US)
Pages (from-to)59-64
Number of pages6
JournalCellular Immunology
Volume185
Issue number1
DOIs
StatePublished - Apr 10 1998
Externally publishedYes

Keywords

  • CSF-1
  • ECM proteins
  • Inflammation

ASJC Scopus subject areas

  • Immunology

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