Abstract
The mesothelium is a flat epithelial lining of serous cavities that could gate the traffic of molecules and cells between the circulation and these body compartments. The present study was designed to elucidate the capacity of mesothelial cells to express adhesion molecules and chemoattractant cytokines, two fundamental mechanisms of regulation of leukocyte recruitment. Cultured human mesothelial cells express appreciable levels of intercellular adhesion molecule 1 (ICAM- 1) and vascular cell adhesion molecule 1 (VCAM-1), and these were increased by in vitro exposure to tumor necrosis factor (TNF), interferon gamma (IFN-gamma), or TNF and IFN-gamma. Interleukin 1 (IL- 1) was a less consistent stimulus for adhesion molecule expression in vitro. Unlike endothelial cells, used as a reference cell population, resting or stimulated mesothelial cells did not express E-selectin and ICAM-2, as assessed by flow cytometry. Analysis of VCAM-1 mRNA by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that mesothelial cells expressed both the seven- and the six-Ig domain transcripts, with predominance of the longer species. Monocytes bound appreciably to "resting" and, to a greater extent, to stimulated mesothelial cells. Monocytes exposed to IFN-gamma and lipopolysaccharide, used as prototypic activation signals, showed increased capacity to bind mesothelial cells. Anti-CD18 monoclonal antibody significantly inhibited binding of monocytes to mesothelial cells, and this blocking effect was amplified by anti-very late antigen 4. Mesothelial cells were able to express the chemotactic cytokines IL- 8 and monocyte chemotactic protein 1 at the mRNA and protein levels. These results indicate that mesothelial cells can express a set of adhesion molecules (ICAM-1 and VCAM-1) overlapping with, but distinct from, that expressed in vascular endothelium (ICAM-1, ICAM-2, VCAM-1, E- selectin), and that these are functionally relevant for interacting with mononuclear phagocytes. The regulated expression of adhesion molecules and chemotactic cytokines by mesothelial cells is probably important in inflammatory and immune reactions that involve serous cavities, such as the long-known macrophage appearance and disappearance reactions.
Full Text
The Full Text of this article is available as a PDF (948.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allavena P., Paganin C., Martin-Padura I., Peri G., Gaboli M., Dejana E., Marchisio P. C., Mantovani A. Molecules and structures involved in the adhesion of natural killer cells to vascular endothelium. J Exp Med. 1991 Feb 1;173(2):439–448. doi: 10.1084/jem.173.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
- Carlos T., Kovach N., Schwartz B., Rosa M., Newman B., Wayner E., Benjamin C., Osborn L., Lobb R., Harlan J. Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells: endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1. Blood. 1991 May 15;77(10):2266–2271. [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Colotta F., Peri G., Villa A., Mantovani A. Rapid killing of actinomycin D-treated tumor cells by human mononuclear cells. I. Effectors belong to the monocyte-macrophage lineage. J Immunol. 1984 Feb;132(2):936–944. [PubMed] [Google Scholar]
- Cybulsky M. I., Fries J. W., Williams A. J., Sultan P., Davis V. M., Gimbrone M. A., Jr, Collins T. Alternative splicing of human VCAM-1 in activated vascular endothelium. Am J Pathol. 1991 Apr;138(4):815–820. [PMC free article] [PubMed] [Google Scholar]
- D'Silva H., Yoshida T., Cohen S. The effect of lymphokines on macrophage accumulation and disappearance in the peritoneal cavity. J Exp Pathol. 1983;1(1):61–69. [PubMed] [Google Scholar]
- Dejana E., Bertocchi F., Bortolami M. C., Regonesi A., Tonta A., Breviario F., Giavazzi R. Interleukin 1 promotes tumor cell adhesion to cultured human endothelial cells. J Clin Invest. 1988 Oct;82(4):1466–1470. doi: 10.1172/JCI113753. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Demetri G. D., Zenzie B. W., Rheinwald J. G., Griffin J. D. Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro. Blood. 1989 Aug 15;74(3):940–946. [PubMed] [Google Scholar]
- Dixit V. M., Green S., Sarma V., Holzman L. B., Wolf F. W., O'Rourke K., Ward P. A., Prochownik E. V., Marks R. M. Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. J Biol Chem. 1990 Feb 15;265(5):2973–2978. [PubMed] [Google Scholar]
- Doherty D. E., Haslett C., Tonnesen M. G., Henson P. M. Human monocyte adherence: a primary effect of chemotactic factors on the monocyte to stimulate adherence to human endothelium. J Immunol. 1987 Mar 15;138(6):1762–1771. [PubMed] [Google Scholar]
- Elices M. J., Osborn L., Takada Y., Crouse C., Luhowskyj S., Hemler M. E., Lobb R. R. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990 Feb 23;60(4):577–584. doi: 10.1016/0092-8674(90)90661-w. [DOI] [PubMed] [Google Scholar]
- Elliott M. J., Gamble J. R., Park L. S., Vadas M. A., Lopez A. F. Inhibition of human monocyte adhesion by interleukin-4. Blood. 1991 Jun 15;77(12):2739–2745. [PubMed] [Google Scholar]
- Elliott M. J., Vadas M. A., Cleland L. G., Gamble J. R., Lopez A. F. IL-3 and granulocyte-macrophage colony-stimulating factor stimulate two distinct phases of adhesion in human monocytes. J Immunol. 1990 Jul 1;145(1):167–176. [PubMed] [Google Scholar]
- Giavazzi R., Garofalo A., Bani M. R., Abbate M., Ghezzi P., Boraschi D., Mantovani A., Dejana E. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice. Cancer Res. 1990 Aug 1;50(15):4771–4775. [PubMed] [Google Scholar]
- Hession C., Tizard R., Vassallo C., Schiffer S. B., Goff D., Moy P., Chi-Rosso G., Luhowskyj S., Lobb R., Osborn L. Cloning of an alternate form of vascular cell adhesion molecule-1 (VCAM1). J Biol Chem. 1991 Apr 15;266(11):6682–6685. [PubMed] [Google Scholar]
- Jonjic N., Jílek P., Bernasconi S., Peri G., Martìn-Padura I., Cenzuales S., Dejana E., Mantovani A. Molecules involved in the adhesion and cytotoxicity of activated monocytes on endothelial cells. J Immunol. 1992 Apr 1;148(7):2080–2083. [PubMed] [Google Scholar]
- Lawrence M. B., Smith C. W., Eskin S. G., McIntire L. V. Effect of venous shear stress on CD18-mediated neutrophil adhesion to cultured endothelium. Blood. 1990 Jan 1;75(1):227–237. [PubMed] [Google Scholar]
- Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
- Lechner J. F., LaVeck M. A., Gerwin B. I., Matis E. A. Differential responses to growth factors by normal human mesothelial cultures from individual donors. J Cell Physiol. 1989 May;139(2):295–300. doi: 10.1002/jcp.1041390211. [DOI] [PubMed] [Google Scholar]
- Mantovani A., Bussolino F., Dejana E. Cytokine regulation of endothelial cell function. FASEB J. 1992 May;6(8):2591–2599. doi: 10.1096/fasebj.6.8.1592209. [DOI] [PubMed] [Google Scholar]
- NELSON D. S., BOYDEN S. V. The loss of macrophages from peritoneal exudates following the injection of antigens into guinea-pigs with delayed-type hypersensitivity. Immunology. 1963 May;6:264–275. [PMC free article] [PubMed] [Google Scholar]
- Nortamo P., Salcedo R., Timonen T., Patarroyo M., Gahmberg C. G. A monoclonal antibody to the human leukocyte adhesion molecule intercellular adhesion molecule-2. Cellular distribution and molecular characterization of the antigen. J Immunol. 1991 Apr 15;146(8):2530–2535. [PubMed] [Google Scholar]
- Oppenheim J. J., Zachariae C. O., Mukaida N., Matsushima K. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu Rev Immunol. 1991;9:617–648. doi: 10.1146/annurev.iy.09.040191.003153. [DOI] [PubMed] [Google Scholar]
- Peri G., Chiaffarino F., Bernasconi S., Padura I. M., Mantovani A. Cytotoxicity of activated monocytes on endothelial cells. J Immunol. 1990 Feb 15;144(4):1444–1448. [PubMed] [Google Scholar]
- Rice G. E., Bevilacqua M. P. An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science. 1989 Dec 8;246(4935):1303–1306. doi: 10.1126/science.2588007. [DOI] [PubMed] [Google Scholar]
- Rollins B. J., Yoshimura T., Leonard E. J., Pober J. S. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am J Pathol. 1990 Jun;136(6):1229–1233. [PMC free article] [PubMed] [Google Scholar]
- Schröder J. M., Christophers E. Secretion of novel and homologous neutrophil-activating peptides by LPS-stimulated human endothelial cells. J Immunol. 1989 Jan 1;142(1):244–251. [PubMed] [Google Scholar]
- Sica A., Matsushima K., Van Damme J., Wang J. M., Polentarutti N., Dejana E., Colotta F., Mantovani A. IL-1 transcriptionally activates the neutrophil chemotactic factor/IL-8 gene in endothelial cells. Immunology. 1990 Apr;69(4):548–553. [PMC free article] [PubMed] [Google Scholar]
- Sica A., Wang J. M., Colotta F., Dejana E., Mantovani A., Oppenheim J. J., Larsen C. G., Zachariae C. O., Matsushima K. Monocyte chemotactic and activating factor gene expression induced in endothelial cells by IL-1 and tumor necrosis factor. J Immunol. 1990 Apr 15;144(8):3034–3038. [PubMed] [Google Scholar]
- Sironi M., Breviario F., Proserpio P., Biondi A., Vecchi A., Van Damme J., Dejana E., Mantovani A. IL-1 stimulates IL-6 production in endothelial cells. J Immunol. 1989 Jan 15;142(2):549–553. [PubMed] [Google Scholar]
- Sonozaki H., Cohen S. The effect of sensitized lymphocytes on peritoneal exudate macrophages in the guinea pig. J Immunol. 1971 May;106(5):1404–1406. [PubMed] [Google Scholar]
- Sonozaki H., Cohen S. The macrophage disappearance reaction: mediation by a soluble lymphocyte-derived factor. Cell Immunol. 1971 Aug;2(4):341–352. doi: 10.1016/0008-8749(71)90069-4. [DOI] [PubMed] [Google Scholar]
- Sonozaki H., Papermaster V., Yoshida T., Cohen S. Desensitization: effects on cutaneous and peritoneal manifestations of delayed hypersensitivity in relation to lymphokine production. J Immunol. 1975 Dec;115(6):1657–1661. [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]
- Strieter R. M., Kunkel S. L., Showell H. J., Remick D. G., Phan S. H., Ward P. A., Marks R. M. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science. 1989 Mar 17;243(4897):1467–1469. doi: 10.1126/science.2648570. [DOI] [PubMed] [Google Scholar]
- Wu Y. J., Parker L. M., Binder N. E., Beckett M. A., Sinard J. H., Griffiths C. T., Rheinwald J. G. The mesothelial keratins: a new family of cytoskeletal proteins identified in cultured mesothelial cells and nonkeratinizing epithelia. Cell. 1982 Dec;31(3 Pt 2):693–703. doi: 10.1016/0092-8674(82)90324-5. [DOI] [PubMed] [Google Scholar]
- de Fougerolles A. R., Stacker S. A., Schwarting R., Springer T. A. Characterization of ICAM-2 and evidence for a third counter-receptor for LFA-1. J Exp Med. 1991 Jul 1;174(1):253–267. doi: 10.1084/jem.174.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Niekerk C. C., Jap P. H., Thomas C. M., Smeets D. F., Ramaekers F. C., Poels L. G. Marker profile of mesothelial cells versus ovarian carcinoma cells. Int J Cancer. 1989 Jun 15;43(6):1065–1071. doi: 10.1002/ijc.2910430619. [DOI] [PubMed] [Google Scholar]