Expression and secretion of type beta transforming growth factor by activated human macrophages.

Abstract

Alveolar macrophages activated with concanavalin A and peripheral blood monocytes activated with lipopolysaccharide secrete type fi transforming growth factor (TGF-j6). There is minimal TGF-/3 secretion in unactivated monocytes, even though TGF-4 mRNA is expressed in these cells at a level similar to that in activated, lipopolysaccharidetreated cultures. U937 lymphoma cells, which have monocytic characteristics, also express mRNA for TGF-j3. Freshly isolated monocytes, both control and lipopolysaccharide-treated, secrete an acid-labile binding protein that inhibits TGF-,B action. We conclude the following: (i) that expression of TGF-1B mRNA is unrelated to monocyte activation, (ii) that secretion of TGF-fJ is induced by monocyte activation, and (iii) that cosecretion of TGF-13 and its monocyte/macrophage-derived binding protein may modulate growth factor action. In contrast, monocytic expression of other growth factor genes, such as the B chain of platelet-derived growth factor, is not constitutive and requires activation.Type , transforming growth factor (TGF-,l) (1-5), a peptide widely distributed in tissues of humans and other animals, has the unusual ability both to stimulate and inhibit the proliferation of cells in culture (6-10). Although the effect of TGF-,B on epithelial cells is consistently inhibitory (6, 7, 9), its role in mesenchymal cell proliferation is more complex (7,8,11). For example, TGF-,3 acts synergistically with epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) to stimulate mitosis of normal rat kidney (NRK) and smooth muscle cells cultured in soft agar yet antagonizes the effect of these mitogens by inhibiting mitosis of the same cells cultured as subconfluent monolayers (7,8,12,13 3 (8).A second cell type that acts as an important source of growth factors during tissue repair in vivo is the macrophage (18). This cell, which appears in healing wounds prior to the onset of a fibrotic response (19,20), is a paracrine source of growth factors. This paracrine role of macrophages during wound repair in vivo can be demonstrated in studies that show that fibrosis is suppressed when monocyte infiltration is blocked (21). Since activated macrophages are known to secrete PDGF (22-24), the present studies were designed to see if macrophages might also be a paracrine source of TGF-P. Both PDGF and TGF-,3 may have important roles in stimulating smooth muscle cell proliferation in atherogenesis (25) as well as in fibroblastic proliferation in connective tissue repair (13, 16). MATERIALS AND METHODSIsolation and Activation of Human Alveolar Macrophages. Alveolar macrophages were obtained by bronchoalveolar lavage of normal nonsmoking human volunteers; samples typically contained >90% alveolar macrophages, -8% lymphocytes, and <1% polymorphonuclear leukocytes (26). Alveolar macrophages were suspended (106 cells per ml) in serum-free medium [MCDB 104/Dulbecco Vogt phosphatebuffered saline (PBS), 1:1 (vol/vol); Irvine Scientific and GIBCO, respectively] supplemented with bov...

Overexpression of TGF-β by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer

“…As shown in Figure 7, these TGF-b-positive cells coincided extremely well with that of antigranulocyte antibody-positive cells, and morphological evidence supported a notion that majorities of these cells were neutrophils (Figure 8). Together with previous reports that TGF-b is distributed in stromal inflammatory cells including granulocytes as well as cancer cells (Roberts et al, 1986;Assoian et al, 1987), it seems reasonable to regard that the predominant source of high levels of TGF-b may be infiltrating neutrophil, though bulk tumoral TGF-b should be accumulation of that from neutrophils, eosinophils and cancer cells. A precise and conclusive cellular source of TGF-b in a tumoral context, however, remains to be identified through in situ hybridisation.…”

“…It then remained to determine the identity of the cells that overexpress TGF-b. We initially postulated that these cells were macrophages, since it has been reported that macrophages can secrete TGF-b (Assoian et al, 1987;Appleton et al, 1993) and, moreover, that the expression of TGF-b is associated with fibroblast collagen synthesis (Khalil et al, 1989). However, while the distribution of TGF-b-positive cells and CD68 þ cells was somewhat similar, double-staining IHC did not show consistent double staining with these two antibodies ( Figure 6).…”

神经肽Y通过Y1受体激活PI3K通路促进RAW264.7细胞中TGF-β1 的产生 周江睿, 徐拯, 蒋春雷

“…Monocytes/macrophages secrete TGF-β1 which, in turn, regulates numerous responses such as monocyte activation, cytokine production, host defense, and chemotaxis [12,14] . Beyond the accumulating evidence implicating TGF-β1 as a potent immunosuppressive agent [18] , recent studies have highlighted the bidirectional effect of this cytokine on monocyte/macrophage function [11,19] .…”

“…It has been reported that lipopolysaccharide (LPS) stimulated human peripheral blood monocytes can induce secretion of TGF-β1 [13] . Further, LPSstimulated murine peritoneal macrophage cells can activate endogenous latent TGF-β1 [14] . These results indicate that LPS-stimulated macrophage cells produce TGF-β1.…”

Preinterventional peak monocyte count and in-stent intimal hyperplasia after coronary stent implantation in human coronary arteries

“…8 There is an increasing evidence from several experimental studies that white blood cells, especially monocytes, play a central role in restenosis after balloon angioplasty and stent implantation. [9][10][11][12] Activated monocytes may contribute to neointimal thickening 12 by generating reactive oxygen species through the production of growth and chemotactic factors, 13 binding to a broad repertoire of ligands, 14 or by matrix metalloproteinase production capable of degrading matrix constituents and consequently facilitating cell migration. 15 Monocytes/macrophages have been demonstrated to be one of the components of the neointima.…”