Abstract
Previous results from our laboratory demonstrated that purified lymphocytosis-promoting factor (LPF), a protein toxin from Bordetella pertussis, inhibited the migration of murine macrophages in vitro. The current study examined the in vivo effects of LPF on mononuclear phagocyte circulation and response to an inflammatory stimulus. Intravenous injection of mice with 200 ng of LPF produced a prolonged monocytosis which peaked with a fivefold increase on day 5 after injection. LPF (200 ng) also inhibited by more than 75% the increase in peritoneal inflammatory macrophages induced by intraperitoneal injection of thioglycolate broth, phytohemagglutinin, or paraffin oil. The inhibition was significant when thioglycolate was given 1 h or 2 or 4 days after LPF but not when thioglycolate was given 2 or 4 days before LPF. The LPF-induced monocytosis on day 5 after injections was not altered by the intraperitoneal injection of thioglycolate broth. The leukocytosis-promoting and macrophage-inhibiting properties of LPF were the same in N:NIH(S) and C3H/HeJ mice. Treatments of LPF that reduced the leukocytosis-promoting effect of LPF also reduced the ability of LPF to inhibit the macrophage response. LPF doses sufficient to induce leukocytosis (greater than or equal to 25 ng) significantly inhibited the thioglycolate-induced increase in peritoneal macrophages. The results indicate that coincident with an LPF-induced monocytosis is a reduction in the number of mononuclear phagocytes at a site of inflammation. An in vivo inhibition of mononuclear phagocyte migration would explain both effects of LPF and is consistent with the in vitro inhibition of macrophage migration by LPF.
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Selected References
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- Benjamin W. R., Klein T. W., Pross S. H., Friedman H. Inhibition of mononuclear phagocyte elongation, migration, and cellular exudate formation following Bordetella pertussis vaccine administration. Proc Soc Exp Biol Med. 1981 Feb;166(2):249–256. doi: 10.3181/00379727-166-41054. [DOI] [PubMed] [Google Scholar]
- Blussé van Oud Alblas A., van der Linden-Schrever B., Van Furth R. Origin and kinetics of pulmonary macrophages during an inflammatory reaction induced by intra-alveolar administration of aerosolized heat-killed BCG. Am Rev Respir Dis. 1983 Aug;128(2):276–281. doi: 10.1164/arrd.1983.128.2.276. [DOI] [PubMed] [Google Scholar]
- Blussé van Oud Alblas A., van der Linden-Schrever B., van Furth R. Origin and kinetics of pulmonary macrophages during an inflammatory reaction induced by intravenous administration of heat-killed bacillus Calmette-Guérin. J Exp Med. 1981 Aug 1;154(2):235–252. doi: 10.1084/jem.154.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bokoch G. M., Katada T., Northup J. K., Hewlett E. L., Gilman A. G. Identification of the predominant substrate for ADP-ribosylation by islet activating protein. J Biol Chem. 1983 Feb 25;258(4):2072–2075. [PubMed] [Google Scholar]
- Braaten B. A., Spangrude G. J., Daynes R. A. Molecular mechanisms of lymphocyte extravasation. II. Studies of in vitro lymphocyte adherence to high endothelial venules. J Immunol. 1984 Jul;133(1):117–122. [PubMed] [Google Scholar]
- Cheers C., Gray D. F. Macrophage behaviour during the complaisant phase of murine pertussis. Immunology. 1969 Dec;17(6):875–887. [PMC free article] [PubMed] [Google Scholar]
- Green G. M., Jakab G. J., Low R. B., Davis G. S. Defense mechanisms of the respiratory membrane. Am Rev Respir Dis. 1977 Mar;115(3):479–514. doi: 10.1164/arrd.1977.115.3.479. [DOI] [PubMed] [Google Scholar]
- Hildebrandt J. D., Sekura R. D., Codina J., Iyengar R., Manclark C. R., Birnbaumer L. Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins. Nature. 1983 Apr 21;302(5910):706–709. doi: 10.1038/302706a0. [DOI] [PubMed] [Google Scholar]
- Imagawa T., Kanoh M., Sonoda S., Utsumi S. Polymorphonuclear leukocyte-inhibitory factor of Bordetella pertussis. III. Inhibition of Arthus reaction and peritoneal infiltration of PMN. Microbiol Immunol. 1980;24(10):895–905. doi: 10.1111/j.1348-0421.1980.tb02895.x. [DOI] [PubMed] [Google Scholar]
- Iwasa S., Yoshikawa T., Fukumura K., Kurokawa M. Effects of the lymphocytosis-promoting factor from Bordetella pertussis on the function and potentiality of lymphocytes. I. Effect on the ability of lymphocytes to recirculate in the body. Jpn J Med Sci Biol. 1970 Feb;23(1):47–60. doi: 10.7883/yoken1952.23.47. [DOI] [PubMed] [Google Scholar]
- Kalpaktsoglou P. K., Yunis E. J., Good R. A. Changes produced by pertussis antigen on the blood cells and lympho-haemapoietic tissues after early and late thymectomy or splenectomy. Clin Exp Immunol. 1969 Jul;5(1):91–103. [PMC free article] [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]
- Levine S., Sowinski R. Inhibition of macrophage response to brain injury. A new effect of pertussis vaccine possibly related to histamine-sensitizing factor. Am J Pathol. 1972 May;67(2):349–360. [PMC free article] [PubMed] [Google Scholar]
- MORSE S. I. STUDIES ON THE LYMPHOCYTOSIS INDUCED IN MICE BY BORDETELLA PERTUSSIS. J Exp Med. 1965 Jan 1;121:49–68. doi: 10.1084/jem.121.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meade B. D., Kind P. D., Ewell J. B., McGrath P. P., Manclark C. R. In vitro inhibition of murine macrophage migration by Bordetella pertussis lymphocytosis-promoting factor. Infect Immun. 1984 Sep;45(3):718–725. doi: 10.1128/iai.45.3.718-725.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morse S. I., Morse J. H. Isolation and properties of the leukocytosis- and lymphocytosis-promoting factor of Bordetella pertussis. J Exp Med. 1976 Jun 1;143(6):1483–1502. doi: 10.1084/jem.143.6.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morse S. I., Riester S. K. Studies on the leukocytosis and lymphocytosis induced by Bordetella pertussis. I. Radioautographic analysis of the circulating cells in mice undergoing pertussis-induced hyperleukocytosis. J Exp Med. 1967 Mar 1;125(3):401–408. doi: 10.1084/jem.125.3.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morse S. I., Riester S. K. Studies on the leukocytosis and lymphocytosis induced by Bordetella pertussis. II. The effect of pertussis vaccine on the thoracic duct lymph and lymphocytes of mice. J Exp Med. 1967 Apr 1;125(4):619–628. doi: 10.1084/jem.125.4.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Munoz J. J., Arai H., Bergman R. K., Sadowski P. L. Biological activities of crystalline pertussigen from Bordetella pertussis. Infect Immun. 1981 Sep;33(3):820–826. doi: 10.1128/iai.33.3.820-826.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murayama T., Ui M. Loss of the inhibitory function of the guanine nucleotide regulatory component of adenylate cyclase due to its ADP ribosylation by islet-activating protein, pertussis toxin, in adipocyte membranes. J Biol Chem. 1983 Mar 10;258(5):3319–3326. [PubMed] [Google Scholar]
- Olson L. C. Pertussis. Medicine (Baltimore) 1975 Nov;54(6):427–469. doi: 10.1097/00005792-197511000-00001. [DOI] [PubMed] [Google Scholar]
- Pittman M., Furman B. L., Wardlaw A. C. Bordetella pertussis respiratory tract infection in the mouse: pathophysiological responses. J Infect Dis. 1980 Jul;142(1):56–66. doi: 10.1093/infdis/142.1.56. [DOI] [PubMed] [Google Scholar]
- Pittman M. Pertussis toxin: the cause of the harmful effects and prolonged immunity of whooping cough. A hypothesis. Rev Infect Dis. 1979 May-Jun;1(3):401–412. doi: 10.1093/clinids/1.3.401. [DOI] [PubMed] [Google Scholar]
- Sato Y., Izumiya K., Sato H., Cowell J. L., Manclark C. R. Aerosol infection of mice with Bordetella pertussis. Infect Immun. 1980 Jul;29(1):261–266. doi: 10.1128/iai.29.1.261-266.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sato Y., Izumiya K., Sato H., Cowell J. L., Manclark C. R. Role of antibody to leukocytosis-promoting factor hemagglutinin and to filamentous hemagglutinin in immunity to pertussis. Infect Immun. 1981 Mar;31(3):1223–1231. doi: 10.1128/iai.31.3.1223-1231.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sekura R. D., Fish F., Manclark C. R., Meade B., Zhang Y. L. Pertussis toxin. Affinity purification of a new ADP-ribosyltransferase. J Biol Chem. 1983 Dec 10;258(23):14647–14651. [PubMed] [Google Scholar]
- Spangrude G. J., Braaten B. A., Daynes R. A. Molecular mechanisms of lymphocyte extravasation. I. Studies of two selective inhibitors of lymphocyte recirculation. J Immunol. 1984 Jan;132(1):354–362. [PubMed] [Google Scholar]
- Taub R. N., Rosett W., Adler A., Morse S. I. Distribution of labeled lymph node cells in mice during the lymphocytosis induced by Bordetella pertussis. J Exp Med. 1972 Dec 1;136(6):1581–1593. doi: 10.1084/jem.136.6.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Unanue E. R. The regulatory role of macrophages in antigenic stimulation. Part Two: symbiotic relationship between lymphocytes and macrophages. Adv Immunol. 1981;31:1–136. doi: 10.1016/s0065-2776(08)60919-0. [DOI] [PubMed] [Google Scholar]
- Van Furth R., Diesselhoff-den Dulk M. C., Mattie H. Quantitative study on the production and kinetics of mononuclear phagocytes during an acute inflammatory reaction. J Exp Med. 1973 Dec 1;138(6):1314–1330. doi: 10.1084/jem.138.6.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Volkman A. Disparity in origin of mononuclear phagocyte populations. J Reticuloendothel Soc. 1976 Apr;19(4):249–268. [PubMed] [Google Scholar]
- Wardlaw A. C., Parton R. Bordetella pertussis toxins. Pharmacol Ther. 1982;19(1):1–53. doi: 10.1016/0163-7258(82)90041-9. [DOI] [PubMed] [Google Scholar]
- Yajima M., Hosoda K., Kanbayashi Y., Nakamura T., Takahashi I., Ui M. Biological properties of islets-activating protein (IAP) purified from the culture medium of Bordetella pertussis. J Biochem. 1978 Jan;83(1):305–312. doi: 10.1093/oxfordjournals.jbchem.a131905. [DOI] [PubMed] [Google Scholar]