Background: It is known that natural killer (NK) cell activity in the lung of smokers (SM) is lower than in non-smokers (NS). However, little is known about the underlying mechanisms. Objective: The purpose of this work was to investigate the mechanisms of the inhibition of NK cell activity by alveolar macrophages (AM) in SM. Methods: Lung effector cells and AM were obtained using bronchoalveolar lavage. The NK cell activity was assayed by 51Cr release method after incubation of 4 and 24 h, using K562 as target cell. AM were added at a concentration of 25% to effector cells. Results: Following 24-hour culture, NK cell activity significantly increased in the NS but not in the SM. Lung NK cell activity was significantly augmented by interleukin-2 in the NS but not in the SM. Addition of AM to the NK cell preparation from SM exerted a significantly greater suppressive effect on autologous blood NK cell activity than in the NS. Indomethacin, catalase or thiourea did not prevent AM-mediated suppression of NK cell activity, in contrast to superoxide dismutase. Conclusions: These results suggest that the suppression of NK cell activity by AM in SM may be caused by O2 release rather than by prostaglandins, H2O2 or OH release from AM.

1.
Barbour SE, Nakashima K, Zhang JB, Tangada S, Hahn CL, Schenkein HA, Tew JG: Tobacco and smoking. Rev Oral Biol Med 1997;8:437–460.
2.
Herberman RB, Djeu JK, Kay HD, Ortaldo JR, Ricardi C, Bonnard CD: Natural killer cells. J Immunol 1979;44:43–70.
3.
Phillips B, Marshall ME, Brown S, Thomspon JS: Effect of smoking on human natural killer cell activity. Cancer 1985;56:2789–2792.
4.
Takeuchi M, Nagai S, Izumi T: Effect of smoking on natural killer cell activity in the lung. Chest 1988;94:688–693.
5.
McCrea KA, Ensor JE, Nall K, Bleecker ER, Hasday JD: Altered cytokine regulation in the lungs of cigarette smokers. Am J Respir Crit Care Med 1994;150:696–703.
6.
Takeuchi M, Nagai S, Izumi T: The mechanism of inhibition of alveolar macrophages on autologous blood natural killer cell activity. Chest 1989;95:383–387.
7.
Hoidal JR, Beall GD, Repine JE: Production of hydroxyl radical by human alveolar macrophages. Infect Immun 1979;26:1088–1094.
8.
Seaman WE, Gindhart TD, Blackman MA, Dalal B, Tolol N, Werb Z: Suppression of natural killing in vitro by monocytes and polymorphonuclear leukocytes. J Clin Invest 1982;69:876–888.
9.
Ortaldo JR, Oldham RK, Cannon GC, Herberman RB: Specificity of natural cytotoxic reactivity of normal human lymphocytes against a myeloid leukemia cell line. J Natl Cancer Inst 1977;59:77–82.
10.
Herberman RB: Natural killer cells and their possible roles in resistance against disease. Clin Immunol Rev 1981;1:1–65.
11.
Gerard JW, Heiner PC, Mink J, Meyers A, Dosman JA: Immunoglobulin levels in smokers and non-smokers. Ann Allergy 1980;44:261–262.
12.
Johnson JD, Houchens DP, Kluwe WM, Craig DK, Fisher GL: Effects of mainstream and environmental tobacco smoke on the immune system in animals and humans. Toxicology 1990;20:369–395.
13.
Miller LG, Goldstein G, Murphy M, Ginns LC: Reversible alterations in immunoregulatory T cells in smoking. Chest 1982;82:526–529.
14.
Costabel U, Bross KJ, Reuter C, Ruhle KH, Matthys H: Alterations in immunoregulatory T-cell subsets in cigarette smokers. Chest 1986;90:39–44.
15.
Hughes DA, Haslam PL, Townshend PJ, Turner-Warwick M: Numerical and function alterations in circulatory lymphocytes in cigarette smokers. Clin Exp Immunol 1985;61:459–466.
16.
Robinson BWS, Pinkston P, Crystal RG: Natural killer cells are present in the normal human lung but are functionally impotent. J Clin Invest 1984;74:942–950.
17.
Itoh K, Shiba K, Shimizu Y, Suzuki R, Kumagai K: Generation of activated killer cells by recombinant interleukin 2 in collaboration with interferon-γ. J Immunol 1985;134:3124–3129.
18.
Morley J, Bray MA, Jones RW, Nugteren DH, Dorp DA: Prostaglandin and thromboxane production by human and guinea-pig macrophages and leukocytes. Prostaglandins 1979;17:730–736.
19.
Weissler JC, Nicod LP, Toews GB: Pulmonary natural killer cell activity is reduced in patients with bronchogenic carcinoma. Am Rev Respir Dis 1987;135:1353–1357.
20.
Richter AM, Abboud RT, Johal SS, Fera TA: Acute effect of smoking on superoxide production by pulmonary alveolar macrophages. Lung 1986;164:233–242.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.