Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1998 Jul;94(3):304–309. doi: 10.1046/j.1365-2567.1998.00518.x

Functional immaturity of rat alveolar macrophages during postnatal development.

J M Bakker 1, E Broug-Holub 1, H Kroes 1, E P van Rees 1, G Kraal 1, J F van Iwaarden 1
PMCID: PMC1364246  PMID: 9767411

Abstract

Alveolar macrophages (AM) are important in the regulation of immune responses in the lung, through their role as scavenger cells and through the production of many bioactive factors. Because in early infancy pulmonary infections are a recurrent problem, we studied the postnatal functional maturation of AM in a rat model. AM were isolated from rat lungs by bronchoalveolar lavage at several time intervals after birth and tested for their ability to ingest Escherichia coli in the presence of surfactant protein A (SP-A). Furthermore, their capacity to produce nitric oxide (NO) and interleukin-1 beta (IL-1 beta) after in vitro lipopolysaccharide (LPS) stimulation was analysed, as well as their capacity to downregulate proliferation of T cells from both mature and neonatal rats. SP-A-mediated phagocytosis of E. coli by AM was reduced in 14-day-old neonatal rats, as compared with mature rats (P < or = 0.05). Also the IL-1 beta production by rat AM after LPS stimulation was impaired at 14 days of age, as compared with IL-1 beta production by AM from mature rats (P < or = 0.05). In contrast, the LPS-induced NO production by rat AM as well as the capacity to inhibit T-cell proliferation were well developed at all ages tested. In conclusion, during postnatal development the rat AM is functionally immature, with respect to phagocytosis and secretion of inflammatory mediators. These differences may underly the enhanced susceptibility to pulmonary infections as found in human neonates.

Full text

PDF
304

Selected References

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

  1. Baughman R. P., Sternberg R. I., Hull W., Buchsbaum J. A., Whitsett J. Decreased surfactant protein A in patients with bacterial pneumonia. Am Rev Respir Dis. 1993 Mar;147(3):653–657. doi: 10.1164/ajrccm/147.3.653. [DOI] [PubMed] [Google Scholar]
  2. Benne C. A., Benaissa-Trouw B., van Strijp J. A., Kraaijeveld C. A., van Iwaarden J. F. Surfactant protein A, but not surfactant protein D, is an opsonin for influenza A virus phagocytosis by rat alveolar macrophages. Eur J Immunol. 1997 Apr;27(4):886–890. doi: 10.1002/eji.1830270413. [DOI] [PubMed] [Google Scholar]
  3. Bessler H., Sirota L., Dulitzky F., Djaldetti M. Production of interleukin-1 by mononuclear cells of newborns and their mothers. Clin Exp Immunol. 1987 Jun;68(3):655–661. [PMC free article] [PubMed] [Google Scholar]
  4. Bessler H., Sirota L., Notti I., Dulitzky F., Djaldetti M. IL-1 beta and IL-3-like activity in preterm infants. Clin Exp Immunol. 1993 Feb;91(2):320–324. doi: 10.1111/j.1365-2249.1993.tb05902.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burchett S. K., Weaver W. M., Westall J. A., Larsen A., Kronheim S., Wilson C. B. Regulation of tumor necrosis factor/cachectin and IL-1 secretion in human mononuclear phagocytes. J Immunol. 1988 May 15;140(10):3473–3481. [PubMed] [Google Scholar]
  6. D'Ambola J. B., Sherman M. P., Tashkin D. P., Gong H., Jr Human and rabbit newborn lung macrophages have reduced anti-Candida activity. Pediatr Res. 1988 Sep;24(3):285–290. doi: 10.1203/00006450-198809000-00001. [DOI] [PubMed] [Google Scholar]
  7. Delacourt C., d'Ortho M. P., Macquin-Mavier I., Pezet S., Housset B., Lafuma C., Harf A. Oxidant-antioxidant balance in alveolar macrophages from newborn rats. Eur Respir J. 1996 Dec;9(12):2517–2524. doi: 10.1183/09031936.96.09122517. [DOI] [PubMed] [Google Scholar]
  8. Derijk R., Berkenbosch F. Development and application of a radioimmunoassay to detect interleukin-1 in rat peripheral circulation. Am J Physiol. 1992 Dec;263(6 Pt 1):E1092–E1098. doi: 10.1152/ajpendo.2006.263.6.E1092. [DOI] [PubMed] [Google Scholar]
  9. Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
  10. Fels A. O., Cohn Z. A. The alveolar macrophage. J Appl Physiol (1985) 1986 Feb;60(2):353–369. doi: 10.1152/jappl.1986.60.2.353. [DOI] [PubMed] [Google Scholar]
  11. Goldstein E., Lippert W., Warshauer D. Pulmonary alveolar macrophage. Defender against bacterial infection of the lung. J Clin Invest. 1974 Sep;54(3):519–528. doi: 10.1172/JCI107788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Griffiss J. M., Schneider H., Mandrell R. E., Yamasaki R., Jarvis G. A., Kim J. J., Gibson B. W., Hamadeh R., Apicella M. A. Lipooligosaccharides: the principal glycolipids of the neisserial outer membrane. Rev Infect Dis. 1988 Jul-Aug;10 (Suppl 2):S287–S295. doi: 10.1093/cid/10.supplement_2.s287. [DOI] [PubMed] [Google Scholar]
  13. Holt P. G., Degebrodt A., O'Leary C., Krska K., Plozza T. T cell activation by antigen-presenting cells from lung tissue digests: suppression by endogenous macrophages. Clin Exp Immunol. 1985 Dec;62(3):586–593. [PMC free article] [PubMed] [Google Scholar]
  14. Holt P. G. Down-regulation of immune responses in the lower respiratory tract: the role of alveolar macrophages. Clin Exp Immunol. 1986 Feb;63(2):261–270. [PMC free article] [PubMed] [Google Scholar]
  15. Holt P. G. Immunoprophylaxis of atopy: light at the end of the tunnel? Immunol Today. 1994 Oct;15(10):484–489. doi: 10.1016/0167-5699(94)90194-5. [DOI] [PubMed] [Google Scholar]
  16. Holt P. G., Oliver J., Bilyk N., McMenamin C., McMenamin P. G., Kraal G., Thepen T. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med. 1993 Feb 1;177(2):397–407. doi: 10.1084/jem.177.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Holt P. G. Postnatal maturation of immune competence during infancy and childhood. Pediatr Allergy Immunol. 1995 May;6(2):59–70. doi: 10.1111/j.1399-3038.1995.tb00261.x. [DOI] [PubMed] [Google Scholar]
  18. Holt P. G., Schon-Hegrad M. A., Oliver J. MHC class II antigen-bearing dendritic cells in pulmonary tissues of the rat. Regulation of antigen presentation activity by endogenous macrophage populations. J Exp Med. 1988 Feb 1;167(2):262–274. doi: 10.1084/jem.167.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kabha K., Schmegner J., Keisari Y., Parolis H., Schlepper-Schaeffer J., Ofek I. SP-A enhances phagocytosis of Klebsiella by interaction with capsular polysaccharides and alveolar macrophages. Am J Physiol. 1997 Feb;272(2 Pt 1):L344–L352. doi: 10.1152/ajplung.1997.272.2.L344. [DOI] [PubMed] [Google Scholar]
  20. Kalina M., Blau H., Riklis S., Kravtsov V. Interaction of surfactant protein A with bacterial lipopolysaccharide may affect some biological functions. Am J Physiol. 1995 Jan;268(1 Pt 1):L144–L151. doi: 10.1152/ajplung.1995.268.1.L144. [DOI] [PubMed] [Google Scholar]
  21. Kradin R. L., McCarthy K. M., Schneeberger E. E. Opsonic receptor function is reduced on the surface of newborn alveolar macrophages. Am Rev Respir Dis. 1986 Feb;133(2):238–244. doi: 10.1164/arrd.1986.133.2.238. [DOI] [PubMed] [Google Scholar]
  22. Kurland G., Cheung A. T., Miller M. E., Ayin S. A., Cho M. M., Ford E. W. The ontogeny of pulmonary defenses: alveolar macrophage function in neonatal and juvenile rhesus monkeys. Pediatr Res. 1988 Mar;23(3):293–297. doi: 10.1203/00006450-198803000-00013. [DOI] [PubMed] [Google Scholar]
  23. Lu C. Y., Unanue E. R. Ontogeny of murine macrophages: functions related to antigen presentation. Infect Immun. 1982 Apr;36(1):169–175. doi: 10.1128/iai.36.1.169-175.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mancilla J., García P., Dinarello C. A. The interleukin-1 receptor antagonist can either reduce or enhance the lethality of Klebsiella pneumoniae sepsis in newborn rats. Infect Immun. 1993 Mar;61(3):926–932. doi: 10.1128/iai.61.3.926-932.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Martin T. R., Ruzinski J. T., Wilson C. B., Skerrett S. J. Effects of endotoxin in the lungs of neonatal rats: age-dependent impairment of the inflammatory response. J Infect Dis. 1995 Jan;171(1):134–144. doi: 10.1093/infdis/171.1.134. [DOI] [PubMed] [Google Scholar]
  26. Maródi L., Káposzta R., Campbell D. E., Polin R. A., Csongor J., Johnston R. B., Jr Candidacidal mechanisms in the human neonate. Impaired IFN-gamma activation of macrophages in newborn infants. J Immunol. 1994 Dec 15;153(12):5643–5649. [PubMed] [Google Scholar]
  27. McCabe R. E., Remington J. S. Mechanisms of killing of Toxoplasma gondii by rat peritoneal macrophages. Infect Immun. 1986 Apr;52(1):151–155. doi: 10.1128/iai.52.1.151-155.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Miller M. E. Phagocyte function in the neonate: selected aspects. Pediatrics. 1979 Nov;64(5 Pt 2 Suppl):709–712. [PubMed] [Google Scholar]
  29. Nelson D. J., Holt P. G. Defective regional immunity in the respiratory tract of neonates is attributable to hyporesponsiveness of local dendritic cells to activation signals. J Immunol. 1995 Oct 1;155(7):3517–3524. [PubMed] [Google Scholar]
  30. Nerurkar L. S., Zeligs B. J., Bellanti J. A. Maturation of the rabbit alveolar macrophage during animal development. II. Biochemical and enzymatic studies. Pediatr Res. 1977 Dec;11(12):1202–1207. doi: 10.1203/00006450-197712000-00007. [DOI] [PubMed] [Google Scholar]
  31. Pikaar J. C., Voorhout W. F., van Golde L. M., Verhoef J., Van Strijp J. A., van Iwaarden J. F. Opsonic activities of surfactant proteins A and D in phagocytosis of gram-negative bacteria by alveolar macrophages. J Infect Dis. 1995 Aug;172(2):481–489. doi: 10.1093/infdis/172.2.481. [DOI] [PubMed] [Google Scholar]
  32. Schuit K. E. Macrophages and resistance of newborn rats to infection. J Reticuloendothel Soc. 1981 Nov;30(5):341–346. [PubMed] [Google Scholar]
  33. Sherman M. P., Lehrer R. I. Oxidative metabolism of neonatal and adult rabbit lung macrophages stimulated with opsonized group B streptococci. Infect Immun. 1985 Jan;47(1):26–30. doi: 10.1128/iai.47.1.26-30.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sherman M. P., Lehrer R. I. Superoxide generation by neonatal and adult rabbit alveolar macrophages. J Leukoc Biol. 1984 Jul;36(1):39–50. doi: 10.1002/jlb.36.1.39. [DOI] [PubMed] [Google Scholar]
  35. Shimizu H., Miyamura K., Kuroki Y. Appearance of surfactant proteins, SP-A and SP-B, in developing rat lung and the effects of in vivo dexamethasone treatment. Biochim Biophys Acta. 1991 Jan 4;1081(1):53–60. doi: 10.1016/0005-2760(91)90249-h. [DOI] [PubMed] [Google Scholar]
  36. Thepen T., Van Rooijen N., Kraal G. Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. J Exp Med. 1989 Aug 1;170(2):499–509. doi: 10.1084/jem.170.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ulich T. R., Yin S. M., Guo K. Z., del Castillo J., Eisenberg S. P., Thompson R. C. The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation. Am J Pathol. 1991 Mar;138(3):521–524. [PMC free article] [PubMed] [Google Scholar]
  38. Ulich T. R., Yin S., Remick D. G., Russell D., Eisenberg S. P., Kohno T. Intratracheal administration of endotoxin and cytokines. IV. The soluble tumor necrosis factor receptor type I inhibits acute inflammation. Am J Pathol. 1993 May;142(5):1335–1338. [PMC free article] [PubMed] [Google Scholar]
  39. Upham J. W., Strickland D. H., Bilyk N., Robinson B. W., Holt P. G. Alveolar macrophages from humans and rodents selectively inhibit T-cell proliferation but permit T-cell activation and cytokine secretion. Immunology. 1995 Jan;84(1):142–147. [PMC free article] [PubMed] [Google Scholar]
  40. Van Iwaarden J. F., Pikaar J. C., Storm J., Brouwer E., Verhoef J., Oosting R. S., van Golde L. M., van Strijp J. A. Binding of surfactant protein A to the lipid A moiety of bacterial lipopolysaccharides. Biochem J. 1994 Oct 15;303(Pt 2):407–411. doi: 10.1042/bj3030407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zeligs B. J., Nerurkar L. S., Bellanti J. A. Maturation of the rabbit alveolar macrophage during animal development. III. Phagocytic and bactericidal functions. Pediatr Res. 1977 Dec;11(12):1208–1211. doi: 10.1203/00006450-197712000-00008. [DOI] [PubMed] [Google Scholar]
  42. Zeligs B. J., Nerurkar L. S., Bellanti J. A., Zeligs J. D. Maturation of the rabbit alveolar macrophage during animal development. I. Perinatal influx into alveoli and ultrastructural differentiation. Pediatr Res. 1977 Mar;11(3 Pt 1):197–208. doi: 10.1203/00006450-197703000-00011. [DOI] [PubMed] [Google Scholar]
  43. van Iwaarden F., Welmers B., Verhoef J., Haagsman H. P., van Golde L. M. Pulmonary surfactant protein A enhances the host-defense mechanism of rat alveolar macrophages. Am J Respir Cell Mol Biol. 1990 Jan;2(1):91–98. doi: 10.1165/ajrcmb/2.1.91. [DOI] [PubMed] [Google Scholar]
  44. van Iwaarden F., Welmers B., Verhoef J., Haagsman H. P., van Golde L. M. Pulmonary surfactant protein A enhances the host-defense mechanism of rat alveolar macrophages. Am J Respir Cell Mol Biol. 1990 Jan;2(1):91–98. doi: 10.1165/ajrcmb/2.1.91. [DOI] [PubMed] [Google Scholar]
  45. van Iwaarden J. F., van Strijp J. A., Ebskamp M. J., Welmers A. C., Verhoef J., van Golde L. M. Surfactant protein A is opsonin in phagocytosis of herpes simplex virus type 1 by rat alveolar macrophages. Am J Physiol. 1991 Aug;261(2 Pt 1):L204–L209. doi: 10.1152/ajplung.1991.261.2.L204. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES