Faculty Research 1990 - 1999

Title

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

Document Type

Article

Publication Date

1998

Keywords

Animal, Cells-Cultured, Cytokines-biosynthesis, Disease-Models-Animal, Dose-Response-Relationship-Immunologic, Extracellular-Matrix-Proteins, Fibronectins, Inflammation: im, Interleukin-6, Kinetics, Macrophage-Activation, Macrophage-Colony-Stimulating-Factor, Macrophages-Peritoneal, Mice, Mice-Inbred-C3H, Mice-Inbred-C57BL, Mice-SCID, Time-Necrosis-factor

JAX Source

Cell Immunol 1998 Apr 10;185(1):59-64

Grant

CA27523/CA/NCI, CA34196/CA/NCI

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 (PM phi), 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 PM phi 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-alpha and GM-CSF proteins were not released. Preincubation of the PM phi 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 PM phi in contact with FN were shown to release TNF-alpha but not GM-CSF. CSF-1 did not enhance VLA 4 (alpha 4 beta 1 or CD49d) but enhanced VLA 5 (alpha 5 beta 1 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 PM phi for differential expression of adhesion molecules that are required for binding to individual ECM proteins and for modulating inflammatory responses of MNP.

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