Airway Hyperresponsiveness after Endotoxin Inhalation Depends on Leukocyte Infiltration

TAKASHI HORIE; CHIHARU OHMORI; SHOZO KOYAMA; OSAMU SAITOH; TAKASHI MUTOH; AKIHARU OKUMA; MASAHITO OKAYASU

doi:10.1620/tjem.156.109

TAKASHI HORIE, CHIHARU OHMORI, SHOZO KOYAMA, OSAMU SAITOH, TAKASHI MUTOH, AKIHARU OKUMA, MASAHITO OKAYASU

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Keywords: bronchoalveolar lavage fluid, hydroxyurea, methacholine, tracheal epithelium

JOURNAL FREE ACCESS

1988 Volume 156 Issue 2 Pages 109-120

DOI https://doi.org/10.1620/tjem.156.109

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Published: 1988 Received: March 10, 1988 Available on J-STAGE: August 31, 2006 Accepted: August 25, 1988 Advance online publication: - Revised: -
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Date of correction: August 31, 2006 Reason for correction: - Correction: ABSTRACT Details: Wrong : HORIE, T., OHMORI, C., KOYAMA, S., SAITOH, O., MUTOH, T., OKUMA, A. and OKAYASU, M. Airway Hyperresponsiveness after Endotoxin Inhalation Depends on Leukocyte Infiltration. Tohoku J. exp. Med., 1988, 156 (2), 109-120 - We have investigated the relationship between acute airway hyperresponsiveness and polymorphonuclear cell (PMN) migration in airways following saline or endotoxin (ET) aerosol inhalation in 63 guinea pigs. In 20 of these animals, granulocytopenia was induced by prior treatment with hydroxyurea (HU). Airway responsiveness (AR) to inhaled methacholine, together with leukocyte counts in bronchoalveolar lavage fluid (BALF) and in tracheal epithelium, was also examined before and at 30min, 1, 3 and 6hr after saline or ET inhalation. In saline inhalation groups, AR and PMN counts in BALF and in tracheal epithelium did not differ from control animals at any time points. However, in ET inhalation groups AR increased significantly at 1 and 3hr and returned to the pre-exposure level at 6hr. This period of hyperresponsiveness was associated with an increment of PMN migration into tracheal epithelium. However, the increment of PMN counts in BALF was delayed to 3 and 6hr after ET. In HU treated animals, AR and PMN counts in BALF and in tracheal epithelium did not change during 6hr after ET inhalation. These results suggest that the hyperresponsiveness induced by ET inhalation either depends upon PMN migration into the tracheal epithelium.
Right : We have investigated the relationship between acute airway hyperresponsiveness and polymorphonuclear cell (PMN) migration in airways following saline or endotoxin (ET) aerosol inhalation in 63 guinea pigs. In 20 of these animals, granulocytopenia was induced by prior treatment with hydroxyurea (HU). Airway responsiveness (AR) to inhaled methacholine, together with leukocyte counts in bronchoalveolar lavage fluid (BALF) and in tracheal epithelium, was also examined before and at 30 min, 1, 3 and 6 hr after saline or ET inhalation. In saline inhalation groups, AR and PMN counts in BALF and in tracheal epithelium did not differ from control animals at any time points. However, in ET inhalation groups AR increased significantly at 1 and 3 hr and returned to the pre-exposure level at 6 hr. This period of hyperresponsiveness was associated with an increment of PMN migration into tracheal epithelium. However, the increment of PMN counts in BALF was delayed to 3 and 6 hr after ET. In HU treated animals, AR and PMN counts in BALF and in tracheal epithelium did not change during 6 hr after ET inhalation. These results suggest that the hyperresponsiveness induced by ET inhalation either depends upon PMN migration into the tracheal epithelium.

Date of correction: August 31, 2006 Reason for correction: - Correction: CITATION Details: Wrong : 1) Ahmed, T., Wasserman, M.A., Muccitelli, R., Tucker, S., Gazeroglu, H. & Marchette, B. (1986) Endotoxin-induced changes in pulmonary hemodynamnics and respiratory mechanics. Amer. Rev. resp. Dis., 134, 1149-1157.
2) Amdur, M.O. & Mead, J. (1958) Mechanics of respiration in unanesthetized guinea pigs. Amer. J. Physiol., 192, 364-368.
3) Boucher, R.C., Pare, P.D. & Hogg, J.C. (1979) Relationship between airway hyperreactivity and hyperpermeability in Ascaris-sensitive monkeys. J. Allergy clin. Immunol., 64, 197-201.
4) Brigham, K.L., Bowers, R.E. & Haynes, J. (1979) Increased sheep lung vascular permeability caused by Escherichia coli endotoxin. Circulat. Res., 45, 292-297.
5) Cockcroft, D.W., Ruffin, R.E., Dolovich, J. & Hargreave, F.E. (1977) Allergen-induced increase in non-allergic bronchial reactivity. clin. Allergy, 7, 503-513.
6) Empey, D.W., Laitinen, L.A., Jacobs, L., Gold, W.M. & Nadel, J.A. (1976) Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection. Amer. Rev. resp. Dis., 113, 131-139.
7) Fabbri, L.M., Aizawa, H., Alpert, S.E., Walters, E.H., O'Byrne, P.M., Gold, B.D., Nadel, J.A. & Holtzman, M.J. (1984) Airway hyperresponsiveness and changes in cell counts in bronchoalveolar lavage after ozone exposure in dogs. Amer. Rev. resp. Dis., 129, 288-291.
8) Golden, J.A., Nadel, J.A. & Boushey, H.A. (1978) Bronchial hyperirritability in healthy subjects after exposure to ozone. Amer. Rev. resp. Dis., 118, 287-294.
9) Gordon, T., Sheppard, D., McDonald, D.M., Distefano, S. & Scypinski, L. (1985) Airway hyperresponsiveness and inflammation induced by toluene diisocyanate in guinea pigs. Amer. Rev. resp. Dis., 132, 1106-1112.
10) Hinson, J.M., Jr., Hutchison, A.A., Brigham, K.L., Meyrick, B.O. & Snapper, J.R. (1984) Effects of granulocyte depletion on pulmonary responsiveness to aerosol histamine. J. appl. Physiol., 56, 411-417.
11) Holtzman, M.J., Cunningham, J.H., Sheller, J.R., Irsigler, G.B., Nadel, J.A. & Boushey, H. A. (1979) Effect of ozone on bronchial reactivity in atopic and nonatopic subjects. Amer. Rev. resp. Dis., 120, 1059-1067.
12) Holtzman, M.J., Fabbri, L.M., O'Byrne, P.M., Gold, B.D., Aizawa, H., Walters, E.H., Alpert, S.E. & Nadel, J.A. (1983a) Importance of airway inflammation for hyperre-sponsiveness induced by ozone. Amer. Rev. resp. Dis., 127, 686-690.
13) Holtzman, M.J., Fabbri, L.M., Skoogh, B.E., O'Byrne, P.M., Walters, E.R., Aizawa, H. & Nadel, J.A. (1983b) Time course of airway hyperresponsiveness induced by ozone in dogs. J. appl. Physiol., 55, 1232-1236.
14) Hudson, A.R., Kilburn, K.H., Halprin, G.M. & McKenzie, W.N. (1977) Granulocyte recruitment to airways exposed to endotoxin aerosols. Amer. Rev. resp. Dis.,115, 89-95.
15) Hulbert, W.C., Walker, D.C., Jackson, A. & Hogg, J.C. (1981) Airway permeability to horseradish peroxidase in guinea pigs: The repair phase after injury by cigarette smoke. Amer. Rev. resp. Dis., 123, 320-326.
16) Hulbert, W.M., McLean, T. & Hogg, J.C. (1985) The effect of acute airway inflammation on bronchial reactivity in guinea pigs. Amer. Rev. resp. Dis., 132, 7-11.
17) Irvin, C.G., Berend, N. & Henson, P.M. (1986) Airways hyperreactivity and inflammation produced by aerosolization of human C5A des arg. Amer. Rev. resp. Dis., 134, 777-783.
18) Lee, L.-Y., Bleecker, E.R. & Nadel, J.A. (1977) Effect of ozone on bronchomotor response to inhaled histamine aerosol in dogs. J. appl. Physiol., 43, 626-631.
19) Little, J.W., Hall, W.J., Douglas, R.G., Jr., Mudholkar, G.S., Speers, D.M. & Patel, K. (1978) Airway hyperreactivity and peripheral airway dysfunction in influenza A infection. Amer. Rev. resp. Dis., 118, 295-303.
20) Marsh, W.R., Irvin, C.G., Murphy, K.R., Behrens, B.Y. & Larsen, G.L. (1985) Increases in airway reactivity to histamine and inflammatory cells in bronchoalveolar lavage after the late asthmatic response in an animal model. Amer. Rev. resp. Dis., 131, 875-879.
21) Meyrick, B. & Brigham, K.L. (1983) Acute effects of Escherichia coli endotoxin on the pulmonary microcirculation of anesthetized sheep. structure: Function relationships. Lab. Invest., 48, 458-470.
22) Murlas, C.G. & Roum, J.H. (1985a) Sequence of pathologic changes in the airway mucosa of guinea pigs during ozone-induced bronchial hyperreactivity. Amer. Rev. resp. Dis., 131, 314-320.
23) Murlas, C. & Roum, J.H. (1985b) Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide. J. appl. Physiol., 58,1630-1637.
24) O'Byrne, P.M., Walters, E.H., Gold, B.D., Aizawa, H.A., Fabbri, L.M., Alpert, S.E., Nadel, J.A. & Holtzman, M.J. (1984) Neutrophil depletion inhibits airway hyperre-sponsiveness induced by ozone exposure. Amer. Rev. resp. Dis., 130, 214-219.
25) O'Byrne, P.M., Leikauf, G.D., Aizawa, H., Bethel, R.A., Ueki, I.F., Holtzman, M.J. & Nadel, J.A. (1985) Leukotriene B₄ induces airway hyperresponsiveness in dogs. J. appl. Physiol., 59, 1941-1946.
26) Okuma, A., Mutoh, T., Kintaka, M., Koyama, S., Majima, T., Yamaguchi, M., Horie, T. & Okayasu, M. (1986) Effect of endotoxin inhalation on airway responsiveness in guinea pigs. Jap. J. thorac. Dis., 24, 423-429. (Japanese)
27) Rylander, R. & Beijer, L. (1987) Inhalation of endotoxin stimulates alveolar macrophage production of platelet-activating factor. Amer. Rev. resp. Dis., 135, 83-86.
28) Snapper, J.R., Hutchison, A.A., Ogletree, M.L. & Brigham, K.L. (1983) Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep. J. clin. Invest., 72, 63-76.
29) Snella, M.-C. & Rylander, R. (1982) Lung cell reactions after inhalation of bacterial lipopolysaccharides. Europ. J. resp. Dis., 63, 550-557.
30) Thompson, J.E., Scypinski, L.A., Gordon, T. & Sheppard, D. (1986) Hydroxyurea inhibits airway hyperresponsiveness in guinea pigs by a granulocyte-independent mechanism. Amer. Rev. resp. Dis., 134, 1213-1218.

Right : 1) Ahmed, T., Wasserman, M. A., Muccitelli, R., Tucker, S., Gazeroglu, H. & Marchette, B. (1986) Endotoxin-induced changes in pulmonary hemodynamnics and respiratory mechanics. Amer. Rev. resp. Dis., 134, 1149-1157.
2) Amdur, M. O. & Mead, J. (1958) Mechanics of respiration in unanesthetized guinea pigs. Amer. J. Physiol., 192, 364-368.
3) Boucher, R. C., Pare, P. D. & Hogg, J. C. (1979) Relationship between airway hyperreactivity and hyperpermeability in Ascaris-sensitive monkeys. J. Allergy clin. Immunol., 64, 197-201.
4) Brigham, K. L., Bowers, R. E. & Haynes, J. (1979) Increased sheep lung vascular permeability caused by Escherichia coli endotoxin. Circulat. Res., 45, 292-297.
5) Cockcroft, D. W., Ruffin, R. E., Dolovich, J. & Hargreave, F. E. (1977) Allergen-induced increase in non-allergic bronchial reactivity. Clin. Allergy, 7, 503-513.
6) Empey, D. W., Laitinen, L. A., Jacobs, L., Gold, W. M. & Nadel, J. A. (1976) Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection. Amer. Rev. resp. Dis., 113, 131-139.
7) Fabbri, L. M., Aizawa, H., Alpert, S. E., Walters, E. H., O'Byrne, P. M., Gold, B. D., Nadel, J. A. & Holtzman, M. J. (1984) Airway hyperresponsiveness and changes in cell counts in bronchoalveolar lavage after ozone exposure in dogs. Amer. Rev. resp. Dis., 129, 288-291.
8) Golden, J. A., Nadel, J. A. & Boushey, H. A. (1978) Bronchial hyperirritability in healthy subjects after exposure to ozone. Amer. Rev. resp. Dis., 118, 287-294.
9) Gordon, T., Sheppard, D., McDonald, D. M., Distefano, S. & Scypinski, L. (1985) Airway hyperresponsiveness and inflammation induced by toluene diisocyanate in guinea pigs. Amer. Rev. resp. Dis., 132, 1106-1112.
10) Hinson, J. M., Jr., Hutchison, A. A., Brigham, K. L., Meyrick, B. O. & Snapper, J. R. (1984) Effects of granulocyte depletion on pulmonary responsiveness to aerosol histamine. J. appl. Physiol., 56, 411-417.
11) Holtzman, M. J., Cunningham, J. H., Sheller, J. R., Irsigler, G. B., Nadel, J. A. & Boushey, H. A. (1979) Effect of ozone on bronchial reactivity in atopic and nonatopic subjects. Amer. Rev. resp. Dis., 120, 1059-1067.
12) Holtzman, M. J., Fabbri, L. M., O'Byrne, P. M., Gold, B. D., Aizawa, H., Walters, E. H., Alpert, S. E. & Nadel, J. A. (1983a) Importance of airway inflammation for hyperresponsiveness induced by ozone. Amer. Rev. resp. Dis., 127, 686-690.
13) Holtzman, M. J., Fabbri, L. M., Skoogh, B. E., O'Byrne, P. M., Walters, E. H., Aizawa, H. & Nadel, J. A. (1983b) Time course of airway hyperresponsiveness induced by ozone in dogs. J. appl. Physiol., 55, 1232-1236.
14) Hudson, A. R., Kilburn, K. H., Halprin, G. M. & McKenzie, W. N. (1977) Granulocyte recruitment to airways exposed to endotoxin aerosols. Amer. Rev. resp. Dis., 115, 89-95.
15) Hulbert, W. C., Walker, D. C., Jackson, A. & Hogg, J. C. (1981) Airway permeability to horseradish peroxidase in guinea pigs: The repair phase after injury by cigarette smoke. Amer. Rev. resp. Dis., 123, 320-326.
16) Hulbert, W. M., McLean, T. & Hogg, J. C. (1985) The effect of acute airway inflammation on bronchial reactivity in guinea pigs. Amer. Rev. resp. Dis., 132, 7-11.
17) Irvin, C. G., Berend, N. & Henson, P. M. (1986) Airways hyperreactivity and inflammation produced by aerosolization of human C5A des arg. Amer. Rev. resp. Dis., 134, 777-783.
18) Lee, L. -Y., Bleecker, E. R. & Nadel, J. A. (1977) Effect of ozone on bronchomotor response to inhaled histamine aerosol in dogs. J. appl. Physiol., 43, 626-631.
19) Little, J. W., Hall, W. J., Douglas, R. G., Jr., Mudholkar, G. S., Speers, D. M. & Patel, K. (1978) Airway hyperreactivity and peripheral airway dysfunction in influenza A infection. Amer. Rev. resp. Dis., 118, 295-303.
20) Marsh, W. R., Irvin, C. G., Murphy, K. R., Behrens, B. Y. & Larsen, G. L. (1985) Increases in airway reactivity to histamine and inflammatory cells in bronchoalveolar lavage after the late asthmatic response in an animal model. Amer. Rev. resp. Dis., 131, 875-879.
21) Meyrick, B. & Brigham, K. L. (1983) Acute effects of Escherichia coli endotoxin on the pulmonary microcirculation of anesthetized sheep. structure: Function relationships. Lab. Invest., 48, 458-470.
22) Murlas. C. G. & Roum, J. H. (1985a) Sequence of pathologic changes in the airway mucosa of guinea pigs during ozone-induced bronchial hyperreactivity. Amer. Rev. resp. Dis., 131, 314-320.
23) Murlas, C. & Roum, J. H. (1985b) Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide. J. appl. Physiol., 58, 1630-1637.
24) O'Byrne, P. M., Walters, E. H., Gold, B. D., Aizawa, H. A., Fabbri, L. M., Alpert, S. E., Nadel, J. A. & Holtzman, M. J. (1984) Neutrophil depletion inhibits airway hyperresponsiveness induced by ozone exposure. Amer. Rev. resp. Dis., 130, 214-219.
25) O'Byrne, P. M., Leikauf, G. D., Aizawa, H., Bethel, R. A., Ueki, I. F., Holtzman, M. J. & Nadel, J. A. (1985) Leukotriene B₄ induces airway hyperresponsiveness in dogs. J. appl. Physiol., 59, 1941-1946.
26) Okuma, A., Mutoh, T., Kintaka, M., Koyama, S., Majima, T., Yamaguchi, M., Horie, T. & Okayasu, M. (1986) Effect of endotoxin inhalation on airway responsiveness in guinea pigs. Jap. J. thorac. Dis., 24, 423-429. (Japanese)
27) Rylander, R. & Beijer, L. (1987) Inhalation of endotoxin stimulates alveolar macrophage production of platelet-activating factor. Amer. Rev. resp. Dis., 135, 83-86.
28) Snapper, J. R., Hutchison, A. A., Ogletree, M. L. & Brigham, K. L. (1983) Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep. J. clin. Invest., 72, 63-76.
29) Snella, M. -C. & Rylander, R. (1982) Lung cell reactions after inhalation of bacterial lipopolysaccharides. Europ. J. resp. Dis., 63, 550-557.
30) Thompson, J. E., Scypinski, L. A., Gordon, T. & Sheppard, D. (1986) Hydroxyurea inhibits airway hyperresponsiveness in guinea pigs by a granulocyte-independent mechanism. Amer. Rev. resp. Dis., 134, 1213-1218.

Date of correction: August 31, 2006 Reason for correction: - Correction: PDF FILE Details: -

Abstract

We have investigated the relationship between acute airway hyperresponsiveness and polymorphonuclear cell (PMN) migration in airways following saline or endotoxin (ET) aerosol inhalation in 63 guinea pigs. In 20 of these animals, granulocytopenia was induced by prior treatment with hydroxyurea (HU). Airway responsiveness (AR) to inhaled methacholine, together with leukocyte counts in bronchoalveolar lavage fluid (BALF) and in tracheal epithelium, was also examined before and at 30 min, 1, 3 and 6 hr after saline or ET inhalation. In saline inhalation groups, AR and PMN counts in BALF and in tracheal epithelium did not differ from control animals at any time points. However, in ET inhalation groups AR increased significantly at 1 and 3 hr and returned to the pre-exposure level at 6 hr. This period of hyperresponsiveness was associated with an increment of PMN migration into tracheal epithelium. However, the increment of PMN counts in BALF was delayed to 3 and 6 hr after ET. In HU treated animals, AR and PMN counts in BALF and in tracheal epithelium did not change during 6 hr after ET inhalation. These results suggest that the hyperresponsiveness induced by ET inhalation either depends upon PMN migration into the tracheal epithelium.

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