Abstract
Legionella micdadei is a human pathogen which survives within leukocytes. To determine how this organism escapes intracellular destruction, we examined its effect on human neutrophil activity. Neutrophils were allowed to ingest L. micdadei prior to evaluation of functional activity. Compared with control cells which did not ingest organisms, cells ingesting L. micdadei showed significantly depressed production of superoxide anion (24.5 +/- 9.0 nmol/10(6) cells per 15 min versus 6.9 +/- 3.2 nmol/10(6) cells per 15 min, respectively; P = 0.002), chemotaxis (43.9 +/- 0.8 mm versus 0.9 +/- 1.3 mm of directed migration, respectively; P = 0.001) and bactericidal activity against Staphylococcus aureus (97.9% versus 37.6% of ingested organisms killed, respectively; P = 0.001). Similar degrees of inhibition could not be demonstrated when either Staphylococcus aureus or Escherichia coli was ingested by cells prior to evaluation. Inhibition of neutrophil function did not occur when phagocytosis of L. micdadei was prevented. However, inhibition occurred with heat-killed as well as with viable organisms. The inhibition of neutrophil function by ingested L. micdadei may help explain the bacterium's ability to survive intracellularly and may begin to explain the pathogenesis of this disease.
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Selected References
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- Babior B. M., Kipnes R. S., Curnutte J. T. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744. doi: 10.1172/JCI107236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Becker E. L., Kermode J. C., Naccache P. H., Yassin R., Marsh M. L., Munoz J. J., Sha'afi R. I. The inhibition of neutrophil granule enzyme secretion and chemotaxis by pertussis toxin. J Cell Biol. 1985 May;100(5):1641–1646. doi: 10.1083/jcb.100.5.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Becker E. L. Leukocyte stimulation: receptor, membrane, and metabolic events. Introduction and summary. Fed Proc. 1986 Jun;45(7):2148–2150. [PubMed] [Google Scholar]
- Bokoch G. M., Gilman A. G. Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin. Cell. 1984 Dec;39(2 Pt 1):301–308. doi: 10.1016/0092-8674(84)90008-4. [DOI] [PubMed] [Google Scholar]
- Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
- Donowitz G. R., Mandell G. L. Monocyte function in patients with chronic granulomatous disease of childhood. Blood. 1982 Nov;60(5):1151–1158. [PubMed] [Google Scholar]
- Friedman R. L., Iglewski B. H., Miller R. D. Identification of a cytotoxin produced by Legionella pneumophila. Infect Immun. 1980 Jul;29(1):271–274. doi: 10.1128/iai.29.1.271-274.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Friedman R. L., Lochner J. E., Bigley R. H., Iglewski B. H. The effects of Legionella pneumophila toxin on oxidative processes and bacterial killing of human polymorphonuclear leukocytes. J Infect Dis. 1982 Sep;146(3):328–334. doi: 10.1093/infdis/146.3.328. [DOI] [PubMed] [Google Scholar]
- Gilman A. G. G proteins and dual control of adenylate cyclase. Cell. 1984 Mar;36(3):577–579. doi: 10.1016/0092-8674(84)90336-2. [DOI] [PubMed] [Google Scholar]
- Hallett M. B., Campbell A. K. Two distinct mechanisms for stimulation of oxygen-radical production by polymorphonuclear leucocytes. Biochem J. 1983 Nov 15;216(2):459–465. doi: 10.1042/bj2160459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hedlund K. W. Legionella toxin. Pharmacol Ther. 1981;15(1):123–130. doi: 10.1016/0163-7258(81)90021-8. [DOI] [PubMed] [Google Scholar]
- Katada T., Ui M. Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein. Proc Natl Acad Sci U S A. 1982 May;79(10):3129–3133. doi: 10.1073/pnas.79.10.3129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lad P. M., Olson C. V., Smiley P. A. Association of the N-formyl-Met-Leu-Phe receptor in human neutrophils with a GTP-binding protein sensitive to pertussis toxin. Proc Natl Acad Sci U S A. 1985 Feb;82(3):869–873. doi: 10.1073/pnas.82.3.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mandell G. L., Hook E. W. Leukocyte function in chronic granulomatous disease of childhood. Studies on a seventeen year old boy. Am J Med. 1969 Sep;47(3):473–486. doi: 10.1016/0002-9343(69)90231-9. [DOI] [PubMed] [Google Scholar]
- Maridonneau-Parini I., Tringale S. M., Tauber A. I. Identification of distinct activation pathways of the human neutrophil NADPH-oxidase. J Immunol. 1986 Nov 1;137(9):2925–2929. [PubMed] [Google Scholar]
- Myerowitz R. L., Pasculle A. W., Dowling J. N., Pazin G. J., Sr, Puerzer M., Yee R. B., Rinaldo C. R., Jr, Hakala T. R. Opportunistic lung infection due to "Pittsburgh Pneumonia Agent". N Engl J Med. 1979 Nov 1;301(18):953–958. doi: 10.1056/NEJM197911013011801. [DOI] [PubMed] [Google Scholar]
- Nelson R. D., Quie P. G., Simmons R. L. Chemotaxis under agarose: a new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes. J Immunol. 1975 Dec;115(6):1650–1656. [PubMed] [Google Scholar]
- Pasculle A. W., Feeley J. C., Gibson R. J., Cordes L. G., Myerowitz R. L., Patton C. M., Gorman G. W., Carmack C. L., Ezzell J. W., Dowling J. N. Pittsburgh pneumonia agent: direct isolation from human lung tissue. J Infect Dis. 1980 Jun;141(6):727–732. doi: 10.1093/infdis/141.6.727. [DOI] [PubMed] [Google Scholar]
- Pasculle A. W., Myerowitz R. L., Rinaldo C. R., Jr New bacterial agent of pneumonia isolated from renal-transplant recipients. Lancet. 1979 Jul 14;2(8133):58–61. doi: 10.1016/s0140-6736(79)90117-x. [DOI] [PubMed] [Google Scholar]
- Rechnitzer C., Kharazmi A., Nielsen H., Baek L. Modulation of human neutrophil and monocyte oxidative burst by Legionella pneumophila sonic extract. Eur J Clin Microbiol. 1987 Dec;6(6):646–652. doi: 10.1007/BF02013061. [DOI] [PubMed] [Google Scholar]
- Rechnitzer C., Kharazmi A., Nielsen H. Effects of Legionella pneumophila sonicate on human neutrophil granulocyte and monocyte chemotaxis. Eur J Clin Invest. 1986 Oct;16(5):368–375. doi: 10.1111/j.1365-2362.1986.tb01011.x. [DOI] [PubMed] [Google Scholar]
- Rogers B. H., Donowitz G. R., Walker G. K., Harding S. A., Sande M. A. Opportunistic pneumonia: a clinicopathological study of five cases caused by an unidentified acid-fast bacterium. N Engl J Med. 1979 Nov 1;301(18):959–961. doi: 10.1056/NEJM197911013011802. [DOI] [PubMed] [Google Scholar]
- Roos D., Bot A. A., van Schaik M. L., de Boer M., Daha M. R. Interaction between human neutrophils and zymosan particles: the role of opsonins and divalent cations. J Immunol. 1981 Feb;126(2):433–440. [PubMed] [Google Scholar]
- Saha A. K., Dowling J. N., LaMarco K. L., Das S., Remaley A. T., Olomu N., Pope M. T., Glew R. H. Properties of an acid phosphatase from Legionella micdadei which blocks superoxide anion production by human neutrophils. Arch Biochem Biophys. 1985 Nov 15;243(1):150–160. doi: 10.1016/0003-9861(85)90783-0. [DOI] [PubMed] [Google Scholar]
- Saha A. K., Dowling J. N., Pasculle A. W., Glew R. H. Legionella micdadei phosphatase catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate in human neutrophils. Arch Biochem Biophys. 1988 Aug 15;265(1):94–104. doi: 10.1016/0003-9861(88)90375-x. [DOI] [PubMed] [Google Scholar]
- Verghese M. W., Smith C. D., Snyderman R. Potential role for a guanine nucleotide regulatory protein in chemoattractant receptor mediated polyphosphoinositide metabolism, Ca++ mobilization and cellular responses by leukocytes. Biochem Biophys Res Commun. 1985 Mar 15;127(2):450–457. doi: 10.1016/s0006-291x(85)80181-9. [DOI] [PubMed] [Google Scholar]
- Weinbaum D. L., Bailey J., Benner R. R., Pasculle A. W., Dowling J. N. The contribution of human neutrophils and serum to host defense against Legionella micdadei. J Infect Dis. 1983 Sep;148(3):510–517. doi: 10.1093/infdis/148.3.510. [DOI] [PubMed] [Google Scholar]
- Weinbaum D. L., Benner R. R., Dowling J. N., Alpern A., Pasculle A. W., Donowitz G. R. Interaction of Legionella micdadei with human monocytes. Infect Immun. 1984 Oct;46(1):68–73. doi: 10.1128/iai.46.1.68-73.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
