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

R Pacifici; A Carano; S A Santoro; L Rifas; J J Jeffrey; J D Malone; R McCracken; L V Avioli

doi:10.1172/JCI114975

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

R Pacifici, A Carano, S A Santoro, L Rifas, J J Jeffrey, J D Malone, R McCracken, and L V Avioli

Published January 1, 1991 - More info

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Abstract

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.

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

R Pacifici, A Carano, S A Santoro, L Rifas, J J Jeffrey, J D Malone, R McCracken, and L V Avioli

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

R Pacifici, A Carano, S A Santoro, L Rifas, J J Jeffrey, J D Malone, R McCracken, and L V Avioli

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