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. 1996 Sep;149(3):953–961.

The membrane attack complex of complement induces interleukin-8 and monocyte chemoattractant protein-1 secretion from human umbilical vein endothelial cells.

K S Kilgore 1, C M Flory 1, B F Miller 1, V M Evans 1, J S Warren 1
PMCID: PMC1865152  PMID: 8780399

Abstract

Cell surface assembly of the membrane attack complex (MAC) of complement occurs in a variety of pathophysiological settings. Depending upon the density and size distribution of pores formed by the MAC and the functional integrity of membrane regulators of complement activation, the MAC can either cause direct cell lysis or transduce cell activation. We have examined the functional capacity of sublytic concentrations of MAC to induce the secretion of specific alpha- and beta-chemokines from human umbilical vein endothelial cells (HUVECs). Endothelial cell activation by the MAC has particular relevance to complement-dependent inflammatory processes including ischemia-reperfusion injury and acute lung injury. Assembly of sublytic concentrations of the MAC on HUVECs resulted in the sequential secretion of both neutrophil and monocyte chemotactic activities. Analysis of conditioned medium from MAC-bearing HUVECs revealed that the neutrophil chemotactic activity was largely attributable to interleukin (IL)-8, whereas the monocyte chemotactic activity, which was detected later (peak at 8 hours versus 4 hours), was largely attributable to MCP-1. This temporal pattern of MAC-induced secretion of IL-8 and MCP-1 was confirmed using IL-8- and MCP-1-specific enzyme-linked immunosorbent assays. Northern hybridization analysis of HUVECs revealed that MAC deposition was accompanied by an increase in IL-8 and MCP-1 mRNA levels. These data indicate that assembly of sublytic concentrations of the MAC on HUVECs can induce the sequential secretion of both neutrophil and monocyte chemotactic activities and that the former is largely attributable to IL-8 whereas the latter is largely attributable to MCP-1.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baggiolini M., Dahinden C. A. CC chemokines in allergic inflammation. Immunol Today. 1994 Mar;15(3):127–133. doi: 10.1016/0167-5699(94)90156-2. [DOI] [PubMed] [Google Scholar]
  2. Brown Z., Gerritsen M. E., Carley W. W., Strieter R. M., Kunkel S. L., Westwick J. Chemokine gene expression and secretion by cytokine-activated human microvascular endothelial cells. Differential regulation of monocyte chemoattractant protein-1 and interleukin-8 in response to interferon-gamma. Am J Pathol. 1994 Oct;145(4):913–921. [PMC free article] [PubMed] [Google Scholar]
  3. Carney D. F., Lang T. J., Shin M. L. Multiple signal messengers generated by terminal complement complexes and their role in terminal complement complex elimination. J Immunol. 1990 Jul 15;145(2):623–629. [PubMed] [Google Scholar]
  4. Cybulsky A. V. Release of arachidonic acid by complement C5b-9 complex in glomerular epithelial cells. Am J Physiol. 1991 Sep;261(3 Pt 2):F427–F436. doi: 10.1152/ajprenal.1991.261.3.F427. [DOI] [PubMed] [Google Scholar]
  5. Daniels R. H., Houston W. A., Petersen M. M., Williams J. D., Williams B. D., Morgan B. P. Stimulation of human rheumatoid synovial cells by non-lethal complement membrane attack. Immunology. 1990 Feb;69(2):237–242. [PMC free article] [PubMed] [Google Scholar]
  6. Evanoff H. L., Burdick M. D., Moore S. A., Kunkel S. L., Strieter R. M. A sensitive ELISA for the detection of human monocyte chemoattractant protein-1 (MCP-1). Immunol Invest. 1992 Feb;21(1):39–45. doi: 10.3109/08820139209069361. [DOI] [PubMed] [Google Scholar]
  7. Falk R. J., Terrell R. S., Charles L. A., Jennette J. C. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4115–4119. doi: 10.1073/pnas.87.11.4115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Horuk R. The interleukin-8-receptor family: from chemokines to malaria. Immunol Today. 1994 Apr;15(4):169–174. doi: 10.1016/0167-5699(94)90314-X. [DOI] [PubMed] [Google Scholar]
  9. Hänsch G. M., Betz M., Günther J., Rother K. O., Sterzel B. The complement membrane attack complex stimulates the prostanoid production of cultured glomerular epithelial cells. Int Arch Allergy Appl Immunol. 1988;85(1):87–93. doi: 10.1159/000234479. [DOI] [PubMed] [Google Scholar]
  10. Hänsch G. M., Seitz M., Betz M. Effect of the late complement components C5b-9 on human monocytes: release of prostanoids, oxygen radicals and of a factor inducing cell proliferation. Int Arch Allergy Appl Immunol. 1987;82(3-4):317–320. doi: 10.1159/000234216. [DOI] [PubMed] [Google Scholar]
  11. Kilgore K. S., Shen J. P., Miller B. F., Ward P. A., Warren J. S. Enhancement by the complement membrane attack complex of tumor necrosis factor-alpha-induced endothelial cell expression of E-selectin and ICAM-1. J Immunol. 1995 Aug 1;155(3):1434–1441. [PubMed] [Google Scholar]
  12. Korty P. E., Brando C., Shevach E. M. CD59 functions as a signal-transducing molecule for human T cell activation. J Immunol. 1991 Jun 15;146(12):4092–4098. [PubMed] [Google Scholar]
  13. Kunsch C., Lang R. K., Rosen C. A., Shannon M. F. Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL-6. J Immunol. 1994 Jul 1;153(1):153–164. [PubMed] [Google Scholar]
  14. Lovett D. H., Haensch G. M., Goppelt M., Resch K., Gemsa D. Activation of glomerular mesangial cells by the terminal membrane attack complex of complement. J Immunol. 1987 Apr 15;138(8):2473–2480. [PubMed] [Google Scholar]
  15. Marks R. M., Todd R. F., 3rd, Ward P. A. Rapid induction of neutrophil-endothelial adhesion by endothelial complement fixation. Nature. 1989 May 25;339(6222):314–317. doi: 10.1038/339314a0. [DOI] [PubMed] [Google Scholar]
  16. Miller M. D., Krangel M. S. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol. 1992;12(1-2):17–46. [PubMed] [Google Scholar]
  17. Morgan B. P. Complement membrane attack on nucleated cells: resistance, recovery and non-lethal effects. Biochem J. 1989 Nov 15;264(1):1–14. doi: 10.1042/bj2640001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mukaida N., Okamoto S., Ishikawa Y., Matsushima K. Molecular mechanism of interleukin-8 gene expression. J Leukoc Biol. 1994 Nov;56(5):554–558. [PubMed] [Google Scholar]
  19. Nawroth P. P., Bank I., Handley D., Cassimeris J., Chess L., Stern D. Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1363–1375. doi: 10.1084/jem.163.6.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Niculescu F., Rus H., Shin M. L. Receptor-independent activation of guanine nucleotide-binding regulatory proteins by terminal complement complexes. J Biol Chem. 1994 Feb 11;269(6):4417–4423. [PubMed] [Google Scholar]
  21. Pardi R., Inverardi L., Bender J. R. Regulatory mechanisms in leukocyte adhesion: flexible receptors for sophisticated travelers. Immunol Today. 1992 Jun;13(6):224–230. doi: 10.1016/0167-5699(92)90159-5. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Schall T. J. Biology of the RANTES/SIS cytokine family. Cytokine. 1991 May;3(3):165–183. doi: 10.1016/1043-4666(91)90013-4. [DOI] [PubMed] [Google Scholar]
  24. Suttorp N., Seeger W., Zinsky S., Bhakdi S. Complement complex C5b-8 induces PGI2 formation in cultured endothelial cells. Am J Physiol. 1987 Jul;253(1 Pt 1):C13–C21. doi: 10.1152/ajpcell.1987.253.1.C13. [DOI] [PubMed] [Google Scholar]
  25. Taub D. D., Oppenheim J. J. Review of the chemokine meeting the Third International Symposium of Chemotactic Cytokines. Cytokine. 1993 May;5(3):175–179. doi: 10.1016/1043-4666(93)90001-l. [DOI] [PubMed] [Google Scholar]
  26. Ueda A., Okuda K., Ohno S., Shirai A., Igarashi T., Matsunaga K., Fukushima J., Kawamoto S., Ishigatsubo Y., Okubo T. NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene. J Immunol. 1994 Sep 1;153(5):2052–2063. [PubMed] [Google Scholar]
  27. Varki A. Selectins and other mammalian sialic acid-binding lectins. Curr Opin Cell Biol. 1992 Apr;4(2):257–266. doi: 10.1016/0955-0674(92)90041-a. [DOI] [PubMed] [Google Scholar]
  28. Vogt W., Hesse D. Activation of the fifth component of human complement by oxygen-derived free radicals, and by methionine oxidizing agents: a comparison. Immunobiology. 1992 Apr;184(4-5):384–391. doi: 10.1016/S0171-2985(11)80595-4. [DOI] [PubMed] [Google Scholar]
  29. Vogt W., Zimmermann B., Hesse D., Nolte R. Activation of the fifth component of human complement, C5, without cleavage, by methionine oxidizing agents. Mol Immunol. 1992 Feb;29(2):251–256. doi: 10.1016/0161-5890(92)90106-8. [DOI] [PubMed] [Google Scholar]
  30. Väkevä A., Laurila P., Meri S. Regulation of complement membrane attack complex formation in myocardial infarction. Am J Pathol. 1993 Jul;143(1):65–75. [PMC free article] [PubMed] [Google Scholar]
  31. Ward P. A., Marks R. M. The acute inflammatory reaction. Curr Opin Immunol. 1989 Oct;2(1):5–9. doi: 10.1016/0952-7915(89)90090-3. [DOI] [PubMed] [Google Scholar]
  32. Warren J. S., Ward P. A., Johnson K. J. Tumor necrosis factor: a plurifunctional mediator of acute inflammation. Mod Pathol. 1988 May;1(3):242–247. [PubMed] [Google Scholar]
  33. Wiedmer T., Ando B., Sims P. J. Complement C5b-9-stimulated platelet secretion is associated with a Ca2+-initiated activation of cellular protein kinases. J Biol Chem. 1987 Oct 5;262(28):13674–13681. [PubMed] [Google Scholar]
  34. Zimmerman G. A., Prescott S. M., McIntyre T. M. Endothelial cell interactions with granulocytes: tethering and signaling molecules. Immunol Today. 1992 Mar;13(3):93–100. doi: 10.1016/0167-5699(92)90149-2. [DOI] [PubMed] [Google Scholar]

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