Bone matrix constituents stimulate interleukin-1 release from human blood mononuclear cells.

Pacifici R, Carano A, Santoro SA, Rifas L, Jeffrey JJ, Malone JD, McCracken R, Avioli LV
J Clin Invest. 1991 87 (1): 221-8

PMID: 1845868 · PMCID: PMC295032 · DOI:10.1172/JCI114975

To test the hypothesis that mononuclear cells are stimulated to release interleukin 1 (IL-1) by bone fragments released in the bone microenvironment during the remodeling cycle, we have investigated the effects of bone matrix and some of its constituents on IL-1 secretin from peripheral blood mononuclear cells (PBMC). Increases in IL-1 activity were observed when either PBMC or adherent monocytes, but not lymphocytes depleted of monocytes, were co-cultured with either human or rat bone particles but not with latex particles of similar size. Co-culture of PBMC with bone particles in a transwell system where the cells were physically separated from the bone particles, or with osteoblast- or osteoclast-covered bone particles, did not stimulate IL-1 release, indicating that a physical contact between PBMC and the bone surface is required for eliciting IL-1 release. This was confirmed by the finding of a lower stimulatory effect of bone particles pretreated with etidronate, a bisphosphonate which decreases the bone binding capacity of PBMC. Constituents of bone matrix, such as collagen fragments, hydroxyproline, and, to a lesser extent, transforming growth factor-beta, but not osteocalcin, alpha 2HS glycoprotein, fragments of either bone sialoprotein or osteopontin, and fibronectin, stimulated PBMC IL-1 release in a dose-dependent fashion. Collagen-stimulated IL-1 release was partially and specifically inhibited by a monoclonal antibody directed against the alpha 2 beta 1-integrin cell surface collagen receptor. These data demonstrate that products of bone resorption, known to be chemotactic for mononuclear cells, stimulate PBMC IL-1 activity. These findings may help explain previous documentation of increased IL-1 secretion by circulating monocytes obtained from patients with high turnover osteoporosis.

MeSH Terms (18)

Animals Antibodies, Monoclonal Bone Matrix Bone Resorption Cell Adhesion Cells, Cultured Collagen Durapatite Etidronic Acid Guinea Pigs Humans Hydroxyapatites Interleukin-1 Leukocytes, Mononuclear Polymyxin B Rats Receptors, Cell Surface Receptors, Collagen

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