Skip to main content
PMC home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1982 Sep;35(9):972–979. doi: 10.1136/jcp.35.9.972

Monocyte function in cirrhosis.

G Holdstock, B Leslie, S Hill, A Tanner, R Wright
PMCID: PMC497847  PMID: 7119129

Abstract

Monocyte function has been studied in a total of 51 patients with biopsy-proven cirrhosis and 35 controls. There was significantly reduced monocyte spreading (p less than 0.05), chemotaxis (p less than 0.02), bacterial phagocytosis (p less than 0.05) and bacterial killing (p less than 0.02) in the cirrhotics compared to the controls. Monocytes from patients with cirrhosis produced significantly less of the lysosomal enzymes N-acetyl beta-glucosaminidase and beta-glucuronidase than those obtained from the controls (p less than 0.02). There was no significant difference in the number of monocytes obtained, the number of macrophage precursors, and the nitro-blue tetrazoline (NBT) reduction between the cirrhotic and the controls. The reduced function appeared to be mainly due to a circulating inhibitory factor and could be corrected by incubation of the cirrhotic cells in serum from control subjects. The response of monocytes from patients with cirrhosis did not differ from the controls in their response to added endotoxin or latex particles suggesting that they are capable of a normal response in the absence of the inhibitory factor. Paired specimens of portal and systemic serum were collected from patients with no evidence of liver disease undergoing vascular surgery. When added to normal human monocytes the portal serum caused a significant reduction in bacterial killing (p less than 0.02) and chemotaxis (p less than 0.05) compared to results obtained in the paired systemic serum. Mixing experiments suggests the presence of an active inhibitor in the portal serum. The results suggest that monocyte function is reduced in cirrhosis apparently due to a serum inhibitor which may have originated from the portal vein. The abnormalities may account in part for the increased susceptibility of these patients to infection.

Full text

PDF
974

Selected References

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

  1. BOYDEN S. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med. 1962 Mar 1;115:453–466. doi: 10.1084/jem.115.3.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baehner R. L., Nathan D. G. Quantitative nitroblue tetrazolium test in chronic granulomatous disease. N Engl J Med. 1968 May 2;278(18):971–976. doi: 10.1056/NEJM196805022781801. [DOI] [PubMed] [Google Scholar]
  3. Beutler E., Kuhl W., Matsumoto F., Pangalis G. Acid hydrolases in leukocytes and platelets of normal subjects and in patients with Gaucher's and Fabry's disease. J Exp Med. 1976 Apr 1;143(4):975–980. doi: 10.1084/jem.143.4.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bjorneboe M., Prytz H., Orskov F. Antibodies to intestinal microbes in serum of patients with cirrhosis of the liver. Lancet. 1972 Jan 8;1(7741):58–60. doi: 10.1016/s0140-6736(72)90060-8. [DOI] [PubMed] [Google Scholar]
  5. Brayton R. G., Stokes P. E., Schwartz M. S., Louria D. B. Effect of alcohol and various diseases on leukocyte mobilization, phagocytosis and intracellular bacterial killing. N Engl J Med. 1970 Jan 15;282(3):123–128. doi: 10.1056/NEJM197001152820303. [DOI] [PubMed] [Google Scholar]
  6. Currie G. A., Hedley D. W. Monocytes and macrophages in malignant melanoma. I. Peripheral blood macrophage precursors. Br J Cancer. 1977 Jul;36(1):1–6. doi: 10.1038/bjc.1977.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DeMeo A. N., Andersen B. R. Defective chemotaxis associated with a serum inhibitor in cirrhotic patients. N Engl J Med. 1972 Apr 6;286(14):735–740. doi: 10.1056/NEJM197204062861401. [DOI] [PubMed] [Google Scholar]
  8. Eichner E. R. The hematologic disorders of alcoholism. Am J Med. 1973 May;54(5):621–630. doi: 10.1016/0002-9343(73)90120-4. [DOI] [PubMed] [Google Scholar]
  9. Ferluga J., Allison A. C. Role of mononuclear infiltrating cells in pathogenesis of hepatitis. Lancet. 1978 Sep 16;2(8090):610–611. doi: 10.1016/s0140-6736(78)92828-3. [DOI] [PubMed] [Google Scholar]
  10. Fierer J., Finley F. Deficient serum bactericidal activity against Escherichia coli in patients with cirrhosis of the liver. J Clin Invest. 1979 May;63(5):912–921. doi: 10.1172/JCI109391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. GREEN G. M., KASS E. H. FACTORS INFLUENCING THE CLEARANCE OF BACTERIA BY THE LUNG. J Clin Invest. 1964 Apr;43:769–776. doi: 10.1172/JCI104961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ganguly N. K., Kingham J. G., Lloyd B., Lloyd R. S., Price C. P., Triger D. R., Wright R. Acid hydrolases in monocytes from patients with inflammatory bowel disease, chronic liver disease, and rheumatoid arthritis. Lancet. 1978 May 20;1(8073):1073–1075. doi: 10.1016/s0140-6736(78)90917-0. [DOI] [PubMed] [Google Scholar]
  13. Hassner A., Kletter Y., Shlag D., Yedvab M., Aronson M., Shibolet S. Impaired monocyte function in liver cirrhosis. Br Med J (Clin Res Ed) 1981 Apr 18;282(6272):1262–1263. doi: 10.1136/bmj.282.6272.1262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hedley D. W., Currie G. A. Monocytes and macrophages in malignant melanoma. III. Reduction of nitroblue tetrazolium by peripheral blood monocytes. Br J Cancer. 1978 May;37(5):747–752. doi: 10.1038/bjc.1978.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. McCarthy J. B., Wahl S. M., Rees J. C., Olsen C. E., Sandberg L., Wahl L. M. Mediation of macrophage collagenase production by 3'-5' cyclic adenosine monophosphate. J Immunol. 1980 May;124(5):2405–2409. [PubMed] [Google Scholar]
  17. Musson R. A., Shafran H., Henson P. M. Intracellular levels and stimulated release of lysosomal enzymes from human peripheral blood monocytes and monocyte-derived macrophages. J Reticuloendothel Soc. 1980 Sep;28(3):249–264. [PubMed] [Google Scholar]
  18. Nolan J. P. The role of endotoxin in liver injury. Gastroenterology. 1975 Dec;69(6):1346–1356. [PubMed] [Google Scholar]
  19. North R. J. The concept of the activated macrophage. J Immunol. 1978 Sep;121(3):806–809. [PMC free article] [PubMed] [Google Scholar]
  20. O'Keefe S. J., El-Zayadi A. R., Carraher T. E., Davis M., Williams R. Malnutrition and immuno-incompetence in patients with liver disease. Lancet. 1980 Sep 20;2(8195 Pt 1):615–617. doi: 10.1016/s0140-6736(80)90284-6. [DOI] [PubMed] [Google Scholar]
  21. Reiner R. G., Tanner A. R., Keyhani A. H., Wright R. A comparative study of lysosomal enzyme activity in monocytes and Kupffer cells isolated simultaneously in a rat model of liver injury. Clin Exp Immunol. 1981 Feb;43(2):376–380. [PMC free article] [PubMed] [Google Scholar]
  22. Rinehart J. J., Sagone A. L., Balcerzak S. P., Ackerman G. A., LoBuglio A. F. Effects of corticosteroid therapy on human monocyte function. N Engl J Med. 1975 Jan 30;292(5):236–241. doi: 10.1056/NEJM197501302920504. [DOI] [PubMed] [Google Scholar]
  23. SANFORD K. K., EARLE W. R., EVANS V. J., WALTZ H. K., SHANNON J. E. The measurement of proliferation in tissue cultures by enumeration of cell nuclei. J Natl Cancer Inst. 1951 Feb;11(4):773–795. [PubMed] [Google Scholar]
  24. Segal A. W., Peters T. J. The nylon column dye test: a possible screening test of phagocyte function. Clin Sci Mol Med. 1975 Dec;49(6):591–596. doi: 10.1042/cs0490591. [DOI] [PubMed] [Google Scholar]
  25. Steigbigel R. T., Lambert L. H., Jr, Remington J. S. Phagocytic and bacterial properties of normal human monocytes. J Clin Invest. 1974 Jan;53(1):131–142. doi: 10.1172/JCI107531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tanner A., Keyhani A., Reiner R., Holdstock G., Wright R. Proteolytic enzymes released by liver macrophages may promote hepatic injury in a rat model of hepatic damage. Gastroenterology. 1981 Apr;80(4):647–654. [PubMed] [Google Scholar]
  27. Territo M. C., Cline M. J. Monocyte function in man. J Immunol. 1977 Jan;118(1):187–192. [PubMed] [Google Scholar]
  28. Triger D. R., Alp M. H., Wright R. Bacterial and dietary antibodies in liver disease. Lancet. 1972 Jan 8;1(7741):60–63. doi: 10.1016/s0140-6736(72)90061-x. [DOI] [PubMed] [Google Scholar]
  29. Triger D. R., Boyer T. D., Levin J. Portal and systemic bacteraemia and endotoxaemia in liver disease. Gut. 1978 Oct;19(10):935–939. doi: 10.1136/gut.19.10.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Van Epps D. E., Strickland R. G., Williams R. C., Jr Inhibitors of leukocyte chemotaxis in alcoholic liver disease. Am J Med. 1975 Aug;59(2):200–207. doi: 10.1016/0002-9343(75)90354-x. [DOI] [PubMed] [Google Scholar]
  31. Verbrugh H. A., Peters R., Peterson P. K., Verhoef J. Phagocytosis and killing of staphylococci by human polymorphonuclear and mononuclear leucocytes. J Clin Pathol. 1978 Jun;31(6):539–545. doi: 10.1136/jcp.31.6.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. WHIPPLE R. L., Jr, HARRIS J. F. B. coli septicemia in Laennec's cirrhosis of the liver. Ann Intern Med. 1950 Aug;33(2):462–466. doi: 10.7326/0003-4819-33-2-462. [DOI] [PubMed] [Google Scholar]
  33. Wardle N., Anderson A., James O. Kupffer cell phagocytosis in relation to BSP clearance in liver and inflammatory bowel diseases. Dig Dis Sci. 1980 Jun;25(6):414–419. doi: 10.1007/BF01395504. [DOI] [PubMed] [Google Scholar]
  34. Wyke R. J., Rajkovic I. A., Eddleston A. L., Williams R. Defective opsonisation and complement deficiency in serum from patients with fulminant hepatic failure. Gut. 1980 Aug;21(8):643–649. doi: 10.1136/gut.21.8.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Zigmond S. H., Hirsch J. G. Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor. J Exp Med. 1973 Feb 1;137(2):387–410. doi: 10.1084/jem.137.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES