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

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“…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).…”

Neuropeptide Y promotes TGF-β1 production in RAW264.7 cells by activating PI3K pathway via Y1 receptor

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

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