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. 1992 Mar;89(3):981–988. doi: 10.1172/JCI115681

Tumor necrosis factor mediates experimental pulmonary edema by ICAM-1 and CD18-dependent mechanisms.

S K Lo 1, J Everitt 1, J Gu 1, A B Malik 1
PMCID: PMC442947  PMID: 1347298

Abstract

(TNF alpha)-induced sequestration of neutrophils (PMN) in lungs and of the resultant PMN-dependent pulmonary edema. Guinea pig lungs perfused with Ringers-albumin were challenged with TNF alpha (1,000 U/ml) for 90 min, followed by addition of fresh perfusate containing 2 x 10(7) human PMN. TNF alpha challenge caused sequestration of PMN in the pulmonary vascular bed as indicated by a threefold increase in lung tissue myeloperoxidase activity (MPO). The activation of the sequestered PMN with phorbol 12-myristate 13-acetate (PMA; 5 x 10(-9) M) produced threefold increases in pulmonary artery (Ppa) and pulmonary capillary hydrostatic (Pcap) pressures, and twofold increases in lung wet-to-dry weight (W/D) ratio and capillary filtration coefficient (Kf,c) over baseline. TNF alpha prestimulation was required for these responses since activation of PMN with PMA in control lungs produced smaller increases in Ppa and Pcap (P less than 0.01) and did not change the W/D and Kf,c. TNF alpha prestimulation also induced the expression of intercellular adhesion molecule (ICAM-1) on pulmonary vascular endothelial cells. Monoclonal antibodies (mAbs) to the neutrophil CD18 integrin (beta-chain of CD11/CD18 complex) (mAb IB4) and to its endothelial cell ligand ICAM-1 (mAb RR1/1) were used to examine the role of PMN adhesion in the TNF alpha-induced responses. Pretreatment of PMN with mAb IB4 prevented PMN uptake and increases in Ppa, Pcap, Kf,c, and W/D ratio. Addition of mAb RR1/1 to the perfusate reduced PMN uptake by 58%, and prevented the increases in Ppa, Pcap, Kf,c, and W/D ratio, as with mAb IB4. The findings indicate that TNF alpha prestimulation of lungs mediates PMN uptake and that this requires the expression of ICAM-1 and its interaction with CD18 integrin on PMN. The activation of PMN sequestered by ICAM-1-dependent mechanism contributes to the development of pulmonary vascular injury and edema.

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Selected References

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

  1. Beutler B., Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. doi: 10.1056/NEJM198702123160705. [DOI] [PubMed] [Google Scholar]
  2. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Diamond M. S., Staunton D. E., Marlin S. D., Springer T. A. Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Cell. 1991 Jun 14;65(6):961–971. doi: 10.1016/0092-8674(91)90548-d. [DOI] [PubMed] [Google Scholar]
  4. Diener A. M., Beatty P. G., Ochs H. D., Harlan J. M. The role of neutrophil membrane glycoprotein 150 (Gp-150) in neutrophil-mediated endothelial cell injury in vitro. J Immunol. 1985 Jul;135(1):537–543. [PubMed] [Google Scholar]
  5. Doerschuk C. M., Winn R. K., Coxson H. O., Harlan J. M. CD18-dependent and -independent mechanisms of neutrophil emigration in the pulmonary and systemic microcirculation of rabbits. J Immunol. 1990 Mar 15;144(6):2327–2333. [PubMed] [Google Scholar]
  6. Dustin M. L., Springer T. A. Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol. 1988 Jul;107(1):321–331. doi: 10.1083/jcb.107.1.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ferrante A., Thong Y. H. Optimal conditions for simultaneous purification of mononuclear and polymorphonuclear leucocytes from human blood by the Hypaque-Ficoll method. J Immunol Methods. 1980;36(2):109–117. doi: 10.1016/0022-1759(80)90036-8. [DOI] [PubMed] [Google Scholar]
  8. Gamble J. R., Harlan J. M., Klebanoff S. J., Vadas M. A. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8667–8671. doi: 10.1073/pnas.82.24.8667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gibbs L. S., Lai L., Malik A. B. Tumor necrosis factor enhances the neutrophil-dependent increase in endothelial permeability. J Cell Physiol. 1990 Dec;145(3):496–500. doi: 10.1002/jcp.1041450315. [DOI] [PubMed] [Google Scholar]
  10. Goldblum S. E., Wu K. M., Jay M. Lung myeloperoxidase as a measure of pulmonary leukostasis in rabbits. J Appl Physiol (1985) 1985 Dec;59(6):1978–1985. doi: 10.1152/jappl.1985.59.6.1978. [DOI] [PubMed] [Google Scholar]
  11. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  12. Huang W. M., Gibson S. J., Facer P., Gu J., Polak J. M. Improved section adhesion for immunocytochemistry using high molecular weight polymers of L-lysine as a slide coating. Histochemistry. 1983;77(2):275–279. doi: 10.1007/BF00506570. [DOI] [PubMed] [Google Scholar]
  13. Ismail G., Morganroth M. L., Todd R. F., 3rd, Boxer L. A. Prevention of pulmonary injury in isolated perfused rat lungs by activated human neutrophils preincubated with anti-Mo1 monoclonal antibody. Blood. 1987 Apr;69(4):1167–1174. [PubMed] [Google Scholar]
  14. Kaslovsky R. A., Horgan M. J., Lum H., McCandless B. K., Gilboa N., Wright S. D., Malik A. B. Pulmonary edema induced by phagocytosing neutrophils. Protective effect of monoclonal antibody against phagocyte CD18 integrin. Circ Res. 1990 Oct;67(4):795–802. doi: 10.1161/01.res.67.4.795. [DOI] [PubMed] [Google Scholar]
  15. Lo S. K., Van Seventer G. A., Levin S. M., Wright S. D. Two leukocyte receptors (CD11a/CD18 and CD11b/CD18) mediate transient adhesion to endothelium by binding to different ligands. J Immunol. 1989 Nov 15;143(10):3325–3329. [PubMed] [Google Scholar]
  16. Michie H. R., Manogue K. R., Spriggs D. R., Revhaug A., O'Dwyer S., Dinarello C. A., Cerami A., Wolff S. M., Wilmore D. W. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med. 1988 Jun 9;318(23):1481–1486. doi: 10.1056/NEJM198806093182301. [DOI] [PubMed] [Google Scholar]
  17. Nathan C. F. Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest. 1987 Dec;80(6):1550–1560. doi: 10.1172/JCI113241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pober J. S., Cotran R. S. Cytokines and endothelial cell biology. Physiol Rev. 1990 Apr;70(2):427–451. doi: 10.1152/physrev.1990.70.2.427. [DOI] [PubMed] [Google Scholar]
  19. Pohlman T. H., Stanness K. A., Beatty P. G., Ochs H. D., Harlan J. M. An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-alpha increases neutrophil adherence by a CDw18-dependent mechanism. J Immunol. 1986 Jun 15;136(12):4548–4553. [PubMed] [Google Scholar]
  20. Selig W. M., Noonan T. C., Kern D. F., Malik A. B. Pulmonary microvascular responses to arachidonic acid in isolated perfused guinea pig lung. J Appl Physiol (1985) 1986 Jun;60(6):1972–1979. doi: 10.1152/jappl.1986.60.6.1972. [DOI] [PubMed] [Google Scholar]
  21. Smith C. W., Rothlein R., Hughes B. J., Mariscalco M. M., Rudloff H. E., Schmalstieg F. C., Anderson D. C. Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration. J Clin Invest. 1988 Nov;82(5):1746–1756. doi: 10.1172/JCI113788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Staunton D. E., Dustin M. L., Springer T. A. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature. 1989 May 4;339(6219):61–64. doi: 10.1038/339061a0. [DOI] [PubMed] [Google Scholar]
  24. Tracey K. J., Beutler B., Lowry S. F., Merryweather J., Wolpe S., Milsark I. W., Hariri R. J., Fahey T. J., 3rd, Zentella A., Albert J. D. Shock and tissue injury induced by recombinant human cachectin. Science. 1986 Oct 24;234(4775):470–474. doi: 10.1126/science.3764421. [DOI] [PubMed] [Google Scholar]
  25. 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]

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