Abstract
PBMC express cell surface receptors for extracellular matrix components known as integrins. We have recently shown that ligand binding to one PBMC integrin, the collagen receptor alpha 2 beta 1, stimulates the secretion of interleukin 1 (IL-1). We have now investigated the role of fibronectin (Fn), an adherence protein that has binding sites for both PBMC and collagen, in the generation of the IL-1 response to collagen. In contrast to collagen, Fn did not stimulate IL-1 release but Fn-depleted serum decreased the release of IL-1 induced by collagen. A polyclonal antiserum directed against Fn also decreased the collagen-induced IL-1 secretion. The IL-1 response to collagen from cells incubated in Fn-depleted serum was restored by the addition of either purified Fn or the 120-kD cell-binding fragment of Fn, which contains the cell-binding site but not the collagen-binding domain. Smaller Arg-Gly-Asp (RGD) peptides failed to enhance the PBMC response to collagen but inhibited in a concentration-dependent fashion the potentiating effect Fn. As expected, a MAb against the alpha 2 beta 1 collagen receptor decreased collagen-induced IL-1 release. However collagen-induced IL-1 release was also inhibited by a MAb against the alpha 5 beta 1 Fn receptor. The effect of the two MAbs was not additive, suggesting that the occupancy of both receptors by ligands is required in order for collagen to induce an maximal response from PBMC. The mechanism by which Fn exerts its effect remains unknown. However, flow-cytometric analysis revealed that Fn does not alter expression of the alpha2beta1 receptor on PBMC. These data demonstrate a potentiating effect of Fn on the collagen-induced secretion of IL-1 from human PBMC and suggest that this effect is mediated via the integrin alpha5beta1. These findings indicate a complex interactive role for specific integrin receptors in the regulation of the mononuclear cell immune response.
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Selected References
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- Bonucci E. The organic-inorganic relationships in bone matrix undergoing osteoclastic resorption. Calcif Tissue Res. 1974;16(1):13–36. doi: 10.1007/BF02008210. [DOI] [PubMed] [Google Scholar]
- Clark R. A., DellaPelle P., Manseau E., Lanigan J. M., Dvorak H. F., Colvin R. B. Blood vessel fibronectin increases in conjunction with endothelial cell proliferation and capillary ingrowth during wound healing. J Invest Dermatol. 1982 Nov;79(5):269–276. doi: 10.1111/1523-1747.ep12500076. [DOI] [PubMed] [Google Scholar]
- Clark R. A., Lanigan J. M., DellaPelle P., Manseau E., Dvorak H. F., Colvin R. B. Fibronectin and fibrin provide a provisional matrix for epidermal cell migration during wound reepithelialization. J Invest Dermatol. 1982 Nov;79(5):264–269. doi: 10.1111/1523-1747.ep12500075. [DOI] [PubMed] [Google Scholar]
- Clark R. A., Wikner N. E., Doherty D. E., Norris D. A. Cryptic chemotactic activity of fibronectin for human monocytes resides in the 120-kDa fibroblastic cell-binding fragment. J Biol Chem. 1988 Aug 25;263(24):12115–12123. [PubMed] [Google Scholar]
- Coller B. S. A new murine monoclonal antibody reports an activation-dependent change in the conformation and/or microenvironment of the platelet glycoprotein IIb/IIIa complex. J Clin Invest. 1985 Jul;76(1):101–108. doi: 10.1172/JCI111931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dayer J. M., Ricard-Blum S., Kaufmann M. T., Herbage D. Type IX collagen is a potent inducer of PGE2 and interleukin 1 production by human monocyte macrophages. FEBS Lett. 1986 Mar 31;198(2):208–212. doi: 10.1016/0014-5793(86)80406-9. [DOI] [PubMed] [Google Scholar]
- Dinarello C. A. Biology of interleukin 1. FASEB J. 1988 Feb;2(2):108–115. [PubMed] [Google Scholar]
- Doherty D. E., Henson P. M., Clark R. A. Fibronectin fragments containing the RGDS cell-binding domain mediate monocyte migration into the rabbit lung. A potential mechanism for C5 fragment-induced monocyte lung accumulation. J Clin Invest. 1990 Oct;86(4):1065–1075. doi: 10.1172/JCI114809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dustin M. L., Springer T. A. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989 Oct 19;341(6243):619–624. doi: 10.1038/341619a0. [DOI] [PubMed] [Google Scholar]
- Franceschi R. T., Linson C. J., Peter T. C., Romano P. R. Regulation of cellular adhesion and fibronectin synthesis by 1 alpha,25-dihydroxyvitamin D3. J Biol Chem. 1987 Mar 25;262(9):4165–4171. [PubMed] [Google Scholar]
- Fuhlbrigge R. C., Chaplin D. D., Kiely J. M., Unanue E. R. Regulation of interleukin 1 gene expression by adherence and lipopolysaccharide. J Immunol. 1987 Jun 1;138(11):3799–3802. [PubMed] [Google Scholar]
- Garman R. D., Jacobs K. A., Clark S. C., Raulet D. H. B-cell-stimulatory factor 2 (beta 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7629–7633. doi: 10.1073/pnas.84.21.7629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gowen M., Wood D. D., Ihrie E. J., McGuire M. K., Russell R. G. An interleukin 1 like factor stimulates bone resorption in vitro. Nature. 1983 Nov 24;306(5941):378–380. doi: 10.1038/306378a0. [DOI] [PubMed] [Google Scholar]
- Hasty D. L., Courtney H. S., Simpson W. A., McDonald J. A., Beachey E. H. Immunochemical and ultrastructural mapping of the gelatin-binding and cell-attachment regions of human plasma fibronectin with monoclonal antibodies. J Cell Sci. 1986 Mar;81:125–141. doi: 10.1242/jcs.81.1.125. [DOI] [PubMed] [Google Scholar]
- Heino J., Ignotz R. A., Hemler M. E., Crouse C., Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Concomitant regulation of integrins that share a common beta 1 subunit. J Biol Chem. 1989 Jan 5;264(1):380–388. [PubMed] [Google Scholar]
- Hemler M. E. Adhesive protein receptors on hematopoietic cells. Immunol Today. 1988 Apr;9(4):109–113. doi: 10.1016/0167-5699(88)91280-7. [DOI] [PubMed] [Google Scholar]
- Hynes R. O., Yamada K. M. Fibronectins: multifunctional modular glycoproteins. J Cell Biol. 1982 Nov;95(2 Pt 1):369–377. doi: 10.1083/jcb.95.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ingber D. E., Prusty D., Frangioni J. V., Cragoe E. J., Jr, Lechene C., Schwartz M. A. Control of intracellular pH and growth by fibronectin in capillary endothelial cells. J Cell Biol. 1990 May;110(5):1803–1811. doi: 10.1083/jcb.110.5.1803. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ingber D. E., Prusty D., Frangioni J. V., Cragoe E. J., Jr, Lechene C., Schwartz M. A. Control of intracellular pH and growth by fibronectin in capillary endothelial cells. J Cell Biol. 1990 May;110(5):1803–1811. doi: 10.1083/jcb.110.5.1803. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaplan G., Gaudernack G. In vitro differentiation of human monocytes. Differences in monocyte phenotypes induced by cultivation on glass or on collagen. J Exp Med. 1982 Oct 1;156(4):1101–1114. doi: 10.1084/jem.156.4.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaplan G. In vitro differentiation of human monocytes. Monocytes cultured on glass are cytotoxic to tumor cells but monocytes cultured on collagen are not. J Exp Med. 1983 Jun 1;157(6):2061–2072. doi: 10.1084/jem.157.6.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaye J., Porcelli S., Tite J., Jones B., Janeway C. A., Jr Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells. J Exp Med. 1983 Sep 1;158(3):836–856. doi: 10.1084/jem.158.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kupper T., Horowitz M., Lee F., Robb R., Flood P. M. Autocrine growth of T cells independent of interleukin 2: identification of interleukin 4 (IL 4, BSF-1) as an autocrine growth factor for a cloned antigen-specific helper T cell. J Immunol. 1987 Jun 15;138(12):4280–4287. [PubMed] [Google Scholar]
- Lo S. K., Detmers P. A., Levin S. M., Wright S. D. Transient adhesion of neutrophils to endothelium. J Exp Med. 1989 May 1;169(5):1779–1793. doi: 10.1084/jem.169.5.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDonald J. A., Quade B. J., Broekelmann T. J., LaChance R., Forsman K., Hasegawa E., Akiyama S. Fibronectin's cell-adhesive domain and an amino-terminal matrix assembly domain participate in its assembly into fibroblast pericellular matrix. J Biol Chem. 1987 Mar 5;262(7):2957–2967. [PubMed] [Google Scholar]
- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
- Pacifici R., Carano A., Santoro S. A., Rifas L., Jeffrey J. J., Malone J. D., McCracken R., Avioli L. V. Bone matrix constituents stimulate interleukin-1 release from human blood mononuclear cells. J Clin Invest. 1991 Jan;87(1):221–228. doi: 10.1172/JCI114975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pacifici R., Rifas L., McCracken R., Vered I., McMurtry C., Avioli L. V., Peck W. A. Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2398–2402. doi: 10.1073/pnas.86.7.2398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pacifici R., Rifas L., Teitelbaum S., Slatopolsky E., McCracken R., Bergfeld M., Lee W., Avioli L. V., Peck W. A. Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4616–4620. doi: 10.1073/pnas.84.13.4616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Postlethwaite A. E., Kang A. H. Collagen-and collagen peptide-induced chemotaxis of human blood monocytes. J Exp Med. 1976 Jun 1;143(6):1299–1307. doi: 10.1084/jem.143.6.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raisz L. G. Local and systemic factors in the pathogenesis of osteoporosis. N Engl J Med. 1988 Mar 31;318(13):818–828. doi: 10.1056/NEJM198803313181305. [DOI] [PubMed] [Google Scholar]
- Roberts C. J., Birkenmeier T. M., McQuillan J. J., Akiyama S. K., Yamada S. S., Chen W. T., Yamada K. M., McDonald J. A. Transforming growth factor beta stimulates the expression of fibronectin and of both subunits of the human fibronectin receptor by cultured human lung fibroblasts. J Biol Chem. 1988 Apr 5;263(10):4586–4592. [PubMed] [Google Scholar]
- Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. doi: 10.1172/JCI114957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Senior R. M., Griffin G. L., Mecham R. P. Chemotactic activity of elastin-derived peptides. J Clin Invest. 1980 Oct;66(4):859–862. doi: 10.1172/JCI109926. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shaw L. M., Messier J. M., Mercurio A. M. The activation dependent adhesion of macrophages to laminin involves cytoskeletal anchoring and phosphorylation of the alpha 6 beta 1 integrin. J Cell Biol. 1990 Jun;110(6):2167–2174. doi: 10.1083/jcb.110.6.2167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimizu Y., Van Seventer G. A., Horgan K. J., Shaw S. Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells. Nature. 1990 May 17;345(6272):250–253. doi: 10.1038/345250a0. [DOI] [PubMed] [Google Scholar]
- Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
- Springer T. A., Anderson D. C. The importance of the Mac-1, LFA-1 glycoprotein family in monocyte and granulocyte adherence, chemotaxis, and migration into inflammatory sites: insights from an experiment of nature. Ciba Found Symp. 1986;118:102–126. doi: 10.1002/9780470720998.ch8. [DOI] [PubMed] [Google Scholar]
- Springer T. A., Miller L. J., Anderson D. C. p150,95, the third member of the Mac-1, LFA-1 human leukocyte adhesion glycoprotein family. J Immunol. 1986 Jan;136(1):240–245. [PubMed] [Google Scholar]
- Thorens B., Mermod J. J., Vassalli P. Phagocytosis and inflammatory stimuli induce GM-CSF mRNA in macrophages through posttranscriptional regulation. Cell. 1987 Feb 27;48(4):671–679. doi: 10.1016/0092-8674(87)90245-5. [DOI] [PubMed] [Google Scholar]
- Wayner E. A., Carter W. G. Identification of multiple cell adhesion receptors for collagen and fibronectin in human fibrosarcoma cells possessing unique alpha and common beta subunits. J Cell Biol. 1987 Oct;105(4):1873–1884. doi: 10.1083/jcb.105.4.1873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Werb Z., Tremble P. M., Behrendtsen O., Crowley E., Damsky C. H. Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol. 1989 Aug;109(2):877–889. doi: 10.1083/jcb.109.2.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wood D. D., Cameron P. M. The relationship between bacterial endotoxin and human B cell-activating factor. J Immunol. 1978 Jul;121(1):53–60. [PubMed] [Google Scholar]
- Wright S. D., Meyer B. C. Fibronectin receptor of human macrophages recognizes the sequence Arg-Gly-Asp-Ser. J Exp Med. 1985 Aug 1;162(2):762–767. doi: 10.1084/jem.162.2.762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zardi L., Carnemolla B., Balza E., Borsi L., Castellani P., Rocco M., Siri A. Elution of fibronectin proteolytic fragments from a hydroxyapatite chromatography column. A simple procedure for the purification of fibronectin domains. Eur J Biochem. 1985 Feb 1;146(3):571–579. doi: 10.1111/j.1432-1033.1985.tb08690.x. [DOI] [PubMed] [Google Scholar]
- van Kooyk Y., Weder P., Hogervorst F., Verhoeven A. J., van Seventer G., te Velde A. A., Borst J., Keizer G. D., Figdor C. G. Activation of LFA-1 through a Ca2(+)-dependent epitope stimulates lymphocyte adhesion. J Cell Biol. 1991 Jan;112(2):345–354. doi: 10.1083/jcb.112.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
