Abstract
Staphylococcal enterotoxin A (SEA) is a superantigen, produced by some strains ofStaphylococcus aureus (S. aureus), which can cause a variety of clinical manifestations ranging from food poisoning to shock. SEA can also stimulate human alveolar macrophages to produce interleukin-8 (IL-8), a member of the α-chemokine subfamily that activates and is chemotactic for neutrophils. In these studies we showed that in rabbits, intravenous SEA significantly decreased the circulating white blood cell population from a baseline value of 6409±2027×103 cells/ml to 1943±862×103 cells/ml in 7 h. There was a concommitent increase in IL-8 in the circulating plasma (baseline: 60±34 pg/ml, 7 h post SEA: 109±64 pg/ml). The increase in circulating IL-8 was accompanied by a much greater increase in the IL-8 concentration of the epithelial lining fluid (ELF) where the IL-8 increased from 0.05±0.08 ng/ml (control) to 13.8±9.3 ng/ml (SEA treated). The increase in IL-8 concentration in the alveolar spaces was paralleled by an increase in both the percentage of neutrophils (1.4±0.9% (control) to 26.0±10.8% (SEA treated)) and total number of neutrophils (0.04±0.02×106/ml (control) to 4.8±3.3 106/ml (SEA treated)) in the airspaces, and the numbers of neutrophils in the ELF correlated with the IL-8 concentration r=0.62, p=0.006). When antileukinate, a hexapeptide which inhibits the binding of IL-8 to neutrophils, was administered to animals receiving SEA, the IL-8 concentration in the ELF (14.8±10.7 ng/ml) was not significantly different from the concentration of IL-8 in those animals receiving SEA alone). However, both the percentage of neutrophils (9.5±3.2%), and the total number of neutrophils (1.3±1.0×106/ml) in the ELF following SEA and antileukinate administration was significantly lower than in animals which only received SEA (p<0.05). The findings suggest that SEA released into the circulation during a Staphylococcal infection can cause an inflammatory reaction in the lung. Since this reaction is at least partially mediated by IL-8, antileukinate may have pharmacologic potential in reducing the inflammatory reaction.
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References
Iandolo JJ. Genetic analysis of extracellular toxins of Staphylococcus aureus. Ann Rev Microbiol 1989;43:375–402.
Kunstmann G, Schroder E, Hasbach H, Pulverer G. Immune response to toxic-shock syndrome toxin-1 (TSST-1) and to Staphylococcal enterotoxins A, B and C in Staphylococcus aureus infections. Zbl Bakt 1989;271:486–92.
Johnson HM, Russell JK, Pontzer CH: Staphylococcal enterotoxin superantigens. Proc Soc Exp Biol Med 1991;198:765–71.
Miller EJ, Nagao S, Carr FK, Noble JM, Cohen A. Interleukin-8 (IL-8) is the major neutrophil chemotaxin from human alveolar macrophages stimulated with staphylococcal enterotoxin A (SEA). Inflamm Res 1996;45:386–92.
Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppengeim JJ, et al. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci USA 1987;84:9233–7.
Foster SJ, Aked DM, Schroder J-M, Christophers E. Acute inflammatory effects of a monocyte-derived neutrophil-activating peptide in rabbit skin. Immunol 1989;67:181–3.
Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, et al. interleukin-8 as a macrophage-derived mediator of angiogenesis. Sci 1992;258:1798–801.
Strieter RM, Kunkel SL, Elner VM, Martonyi VM, Koch CL, Polverini PJ, et al. Inlerleukin-8: a corneal factor that induces neovascularization. Am J Pathol 1992;141:1279–84
Miller EJ, Cohen AB, Nagao S, Griffith D, Maunder RJ, Martin TR, et al. Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis 1992;146:427–32.
Miller EJ, Idell S. interleukin-8 (IL-8): An important neutrophil chemotaxin in some cases of exudative pleural effusions. Exp Lung Res 1993;19:589–601.
Miller EJ, Brelsford WG. interleukin-8: the major neutrophil chemotaxin in a case of pseudogout. J Rheumatol 1993;20: 1250–2.
Miller EJ, Cohen AB, Matthay MA. Elevated interleukin-8 levels in the pulmonary edema fluid of patients with ARDS from sepsis. Crit Care Med. In press.
Murphy PM, Tiffany HL. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Sci 1991;253:1280–3.
Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI. Structure and functional expression of a human interleukin-8 receptor. Sci 1991;253:1278.
Hayashi S, Kurdowska A, Miller EJ, Albright ME, Girten BE, Cohen AB. Synthetic hexa- and heptapeptides that inhibit IL-8 from binding to and activating human blood neutrophils. J Immunol 1995;154:814–24.
Peterson BT, Tate RW. Albumin fraction and measurement of total protein concentration. Am J Physiol (Heart Circ Physiol 33) 1993;264:H1723–6.
Peterson BT, Griffith DE, Tate RW, Clancy SW. Single-cycle bronchoalveolar lavage to determine solute concentrations in epithelial lining fluid. Am Rev Respir Dis 1993;147: 1216–22.
Idell S, Kucich U, Fein A, Kueppers F, James HL, Walsh PN, et al. Neutrophil elastase-releasing factors in bronchoalveolar lavage from patients with adult respiratory distress syndrome. Am Rev Respir Dis 1985;132:1090–105.
Weiland JE, Davis WB, Holter JF, Mohammed JR, Dorinsky PM, Gadek JE. Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathological significance. Am Rev Respir Dis 1986;133:218–25.
Hill JD, Ratcliff JL, Parrott JCW, Lamy M, Fallat RJ, Koeniger E, et al. Pulmonary pathology in acute respiratory insufficiency: Lung biopsy as a diagnostic tool. J Thorac Cardiovasc Surg 1982;71:64–71.
Pratt PC. Pathology of adult respiratory distress syndrome: implications regarding therapy. Semin Respir Med 1982;4: 79–85.
Thommasen HV, Boyko WJ, Russell JA, Hogg JC. Transient leukopenia associated with adult respiratory distress syndrome. Lancet 1984;1:809–12.
Bachofen M, Weibel ER. Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicaemia. Am Rev Respir Dis 1977;116:589–615.
Nash G, Foley FD, Langlinais PC. Pulmonary interstitial edema and hyaline membranes in adult burn patients. Hum Pathol 1974;5:149–61.
Harmsen AG: Role of alveolar macrophages in lipopolysaccharide-induced neutrophil accumulation. Infect Immun 1988;56:1858–63.
Kurdowska A, Cohen AB, Carr FK, Stevens MD, Miller EJ, Mullenbach G., et al. Biological and kinetic characterization of recombinant human macrophage inflammatory peptides alpha and beta and comparison with the neutrophil activating peptide 2 and interleukin 8. Cytokine 1993;6:124–34.
Folkesson HG, Matthay MA, Hebert CA, and Broaddus VC. Acid aspiration-induced lung injury in rabbits is mediated by interleukin-8-dependent mechanisms. J Clin Invest 1995; 96:107–16.
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Miller, E.J., Cohen, A.B. & Peterson, B.T. Peptide inhibitor of interleukin-8 (IL-8) reduces staphylococcal enterotoxin-A (SEA) induced neutrophil trafficking to the lung. Inflamm Res 45, 393–397 (1996). https://doi.org/10.1007/BF02252934
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DOI: https://doi.org/10.1007/BF02252934