Mitogenic activity elaborated by macrophage‐like cell lines acts as competence factor(s) for BALB/c 3T3 cells

Wharton, Walker; Gillespie, G. Yancey; Russell, Stephen W.; Pledger, W. J.

doi:10.1002/jcp.1041100115

Cited by 49 publications

(20 citation statements)

References 24 publications

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“…Recently, cells of the monocyte-macrophage series have been shown to release peptides that are mitogenic for fibroblasts, smooth muscle cells, and endothelial cells (18,34,(39)(40)(41)(42)(43) and that may or may not have IL-1 activity (33). Although high-and low-molecular-weight fibroblast growth stimulators have been identified (35), both of these species are larger than the respective high-and low-molecularweight fractions that promote osteoblast growth.…”

Section: Discussionmentioning

confidence: 99%

Macrophage-derived growth factor for osteoblast-like cells and chondrocytes.

Rifas¹,

Shen²,

Mitchell³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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Rat resident peritoneal macrophages in primary culture were found to elaborate a mitogenic factor (or factors) for rat osteoblast-like cells and chondrocytes but not for skin fibroblasts. Growth-promoting activity appeared in the incubation medium within the first 20 hr of macrophage culture and was released in amounts that paralleled the number of macrophages per culture. After their proliferative response, as judged by increases in DNA synthesis and cell number, the osteoblast-like cells became enriched in alkaline phosphatase, an index of osteoblast specialization. The macrophage-derived activity was nondialyzable and heat-stable, and it was eliminated by exposure to trypsin. Inhibition of prostaglandin cyclooxygenase failed to modify its generation. Partial purification (Amicon filter concentration, gel filtration) disclosed principal peaks of activity corresponding to Mr of 43,000 and 10,000. The crude conditioned medium and the Mr 43,000-peak, but not the low-molecular-weight peak, exhibited interleukin 1 activity, as judged by the ability to stimulate the proliferation of mouse thymic lymphocytes. The macrophagederived growth factor described herein may participate in bone remodeling and repair and in primary bone and cartilage growth.The mammalian skeleton is a dynamic tissue, undergoing virtually continuous turnover after its initial development (1). Skeletal turnover stems from a complex remodeling process of microscopic dimensions in which osteoclasts resorb bone mineral and organic matrix and osteoblasts proceed to repair the resorption cavity (2, 3). Resorptive and formative events at each remodeling locus are congruent in space, sequentially coupled in time, and balanced in quantity, so that the mass of bone does not change, at least not in the short term. This spatial, temporal, and quantitative coordination points to the participation of local signals in the control of remodeling, and it has prompted a search for locally elaborated regulatory factors. Cells of the monocyte macrophage series may well generate such factors. Not only are they thought to be the precursors of mature osteoclasts (4-12), they are known to release agents that promote bone resorption both directly and indirectly (13). Furthermore, macrophage-like cells occupy resorption cavities during the time interval between resorption and formation, so that they are appropriately positioned to influence formative events (14,15). We have examined the possibility that macrophages elaborate a factor (or factors) that promote(s) the proliferation of osteoblasts, thereby acting to couple formation and resorption. We describe herein a heat-stable peptide activity in macrophage-conditioned medium (MCM), which promotes the growth of osteoblasts and chondroblasts in vitro. Abbreviations: CDM, chemically defined medium; PDS, plateletpoor plasma-derived serum; IL-1, interleukin 1 (lymphocyte-activating factor); MDGF, macrophage-derived growth factor; MCM, macrophage-conditioned medium. *To whom reprint requests should be addressed. MATER...

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Section: Discussionmentioning

confidence: 99%

Macrophage-derived growth factor for osteoblast-like cells and chondrocytes.

Rifas¹,

Shen²,

Mitchell³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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“…Proliferative responses in cells are induced by two types of growth factor, namely, a competence factor and a progression factor [21]. Cells in GO phase require priming by a competence factor to enter the cell-cycle and a progression factor to synthesize DNA.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Localization of Epidermal Growth Factor and Its Effect on Granulosa Cell Proliferation in Rat Ovary.

1995

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Abstract.The localization of epidermal growth factor (EGF) in the ovary and its effect on proliferation of granulosa cells were investigated in gonadotrophin-primed immature female rats. Immunoreactions with anti-rat EGF monoclonal antibody were observed sparsely in the granulosa layer and antrum of follicles, but not in the theca layer or stromal tissue. The EGF-positive cells were round or oval shaped and often larger than granulosa cells. The localization and morphological appearances of these cells in the follicles were in good agreement with those of macrophages.Although EGF alone did not promote granulosa cell growth in vitro, the labelling index with [3Hlthymidine of granulosa cells cultured with 0.1 ng/ml EGF and 0.1 ng/ml basic fibroblast growth factor was significantly greater than that without the growth factors (18.4% vs. 15.8%, P<0.01). These results suggest that macrophages in follicles may modulate follicular development through a paracrine mechanism by secreting EGF and other growth factors.

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“…Based on a series of experiments, activated monocytes/ macrophages have been claimed to be involved in the regulation of tissue regeneration or repair (7)(8)(9)(10). Animals depleted of monocytes/macrophages show a delay in wound healing (11,12).…”

Section: Introductionmentioning

confidence: 99%

Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin.

Höckel¹,

Jung²,

Vaupel³

et al. 1988

J. Clin. Invest.

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Angiotropin is a differentiation factor for microvascular endothelial cells isolated from serum-free cultures of lectin-activated, porcine monocytes. We used an ear lobe model in rabbits, single intradermal injection of angiotropin to induce phenotypical changes of the endothelial cells in capillaries and postcapillary venules, vascular engorgement, and subsequent angiogenesis in dose-dependent manner. The vascular changes are associated with epidermal and stromal cell proliferation. Angiogenesis and tissue proliferation occur in the absence of tissue necrosis and do not lead to scar formation. Angiotropininduced angiogenesis is not inhibited by local dexamethasone although it involves a defined turnover of inflammatory cells.Proliferation is transient and regressive events follow. The overall tissue reaction resembles changes found in the undamaged skin margin of a primary healing wound during the inflammatory/proliferative phase. From these observations we conclude that angiotropin is an important secretory product of activated peripheral macrophages that triggers inflammatory and proliferative reactions in wound healing by activating microvascular endothelial cells.

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Mitogenic activity elaborated by macrophage‐like cell lines acts as competence factor(s) for BALB/c 3T3 cells

Cited by 49 publications

References 24 publications

Macrophage-derived growth factor for osteoblast-like cells and chondrocytes.

Macrophage-derived growth factor for osteoblast-like cells and chondrocytes.

Immunohistochemical Localization of Epidermal Growth Factor and Its Effect on Granulosa Cell Proliferation in Rat Ovary.

Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin.

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