Neutrophils accumulated in the lung are thought to play a key role in the pathogenesis of adult respiratory distress syndrome and interstitial pneumonia following bone-marrow transplantation. The effects of gabexate mesilate on several aspects of human neutrophil function have been investigated. Gabexate mesilate significantly decreased both the generation of reactive oxygen species (O2−, H202, OH·) by neutrophils and neutrophil chemotaxis. In contrast, the drug did not affect the levels of reactive oxygen species generated by a cell-free reactive-oxygen-species generating system. Intracellular calcium concentrations in neutrophils stimulated by f-Met-Leu-Phe were decreased in the presence of gabexate mesilate. These data suggest that the reduction in reactive-oxygen-species production and neutrophil chemotaxis by gabexate mesilate may contribute to the effectiveness of the drug in adult respiratory distress syndrome and interstitial pneumonia after bone-marrow transplantation. The suppression of the increase in intracellular calcium concentration may at least be responsible for the inhibition of these neutrophil functions by gabexate mesilate.
SaitohYReview of clinical results with gabexate mesilate (Foy) in Japan. FOY Workshop, Dusseldorf. In: Proteinasen-Inhibition (GrözingerKHSchreyAWabnitzRW eds). Dusseldorf: Universitäts Druckerei und Verlag. 1981; pp 108–122.
2.
UmekiSAdachiMWatanabeMGabexate as a therapy for disseminated intravascular coagulation. Arch InternMed1988; 148: 1409–1412.
3.
YasubaHKawaguchiHSatakeNA case of pulmonary aspergillosis complicated with adult respiratory distress syndrome. Nihon Kyobu Rinsho1989; 48: 558–563.
4.
KudoJFuruderaSTanakaKA case of ARDS after subcutaneous bleeding in the patient with chronic alcoholism. Med J Mutual Aid Assoc1986; 35: 437–441.
5.
WakitaHAsaiTHirasawaATreatment with gabexate mesilate for interstitial pneumonia after bone marrow transplantation. Jpn J Inflamm1989; 9: 463–467.
6.
SaidSIFoodaHDPharmacologic modulation of lung injury. Am Rev Respir Dis1989; 139: 1553–1564.
7.
SwankDWMooreSBRoles of the neutrophil and other mediators in adult respiratory distress syndrome. Mayo Clin Proc1989; 64: 1118–1132.
8.
TateRMRepineJENeutrophils and the adult respiratory distress syndrome. Am Rev Respir Dis1983; 128: 552–559.
9.
KadotaJTomonagaAYamadaKSuperoxide production by neutrophils in patients with interstitial and other lung disease. Jpn J Thorac Dis1986; 24: 977–984.
10.
UtsunomiyaTYamamotoTTanakaJThe effect of protease inhibitor on function of human polymorphonuclear cell. Gendai Iryo1986; 18: 1262–1266.
11.
NishizukaYStudies and prospectives of protein kinase C family for cellular regulation. Cancer1989; 63: 1892–1903.
12.
BerridgeMJIrvineRFInositol triphosphate, a novel second messenger in cellular signal transduction. Nature1984; 312: 315–321.
13.
NishizukaYStudies and perspectives of protein kinase C. Science1986; 233: 305–312.
14.
FridovichISuperoxide dismutase in biology and medicine. In: Pathology of Oxygen (AutorAP ed). New York: Academic Press, 1982; p 10.
15.
BorsWSaranMCzapskiGThe nature of intermediates during biological oxygen activation. In: Biological and Clinical Aspects of Superoxide Dismutase (BannisterWHBannisterJV eds). New York: Elsevier, 1980; pp 11–13.
16.
BadweyJAKarnowkyMLActive oxygen species and the functions of phagocytic leukocytes. Ann Rev Biochem1980; 49: 695–726.
17.
RepineJEEatonJWAndersMWGeneration of hydroxyl radical by enzymes, chemicals and human phagocytes in vitro. J Clin Invest1979; 64: 721–725.
18.
WhiteBCAustSDArforsKEBrain injury by ischemic anoxia-hypothesis extension: a tale of two ions. Am J Emerg Med1984; 2: 862–867.
19.
HernandezLGrishamMBGrangerDNA role for iron in oxidant-mediated ischemic injury to intestinal microvasculature. Am J Physiol1987; 253: G49–G53.
20.
NiwaYSakaneTShinguMNeutrophil-generated active oxygens in linear IgA bullous dermatosis. Arch Dermatol1985; 121: 73–78.
21.
SkoseyJLDamgaardEChowDCModification of zymozan-induced release of lysozomal enzymes from polymorphonuclear leukocytes by cytochalasin B. J Cell Biol1974; 62: 625–634.
22.
NelsonRDQuiePGSimmonsRLChemotaxis under agarose. A new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes. J Immunol1977; 115: 1650–1656.
23.
NiwaYSakaneTShinguMEffects of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes—a possible role of increased oxygen radicals generated by neutrophils. J Clin Immunol1983; 3: 228–240.
24.
NiwaYKasamaTMiyachiYNeutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: cross-sectional and longitudinal studies. Life Sci1989; 44: 1655–1664.
25.
JohnstonRBJrLehmeyerJEElaboration of toxic oxygen products by neutrophils and a model of immune complex disease. J Clin Invest1976; 57: 836–841.
26.
MasseyVThe microestimation of succinate and the extinction coefficient of cytochrome c. Biochim Biophys Acta1959; 34: 255–256.
27.
RootRKMetcalfJA H2O2 release from human granulocytes during phagocytosis. J Clin Invest1972; 60: 1266–1279.
28.
KlebanoffSJRosenHEthylene formation by polymorphonuclear leukocytes. J Exp Med1978; 148: 490–505.
29.
JohnsonPCWareJAClivedenPBMeasurement of ionized calcium in blood platelets with the photoprotein aequorin: Comparison with quin 2. J Biol Chem1985; 260: 2069–2076.
30.
GrynkiewiczGPoenieMTsienRY A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem1985; 260: 3440–3450.
31.
OzakiYKumeSFunctional responses of aequorin-loaded human neutrophils. Comparison with fura-2-loaded cells. Biochim Biophys Acta1988; 972: 113–119.
32.
NiwaYMiyachiYSakaneT Methyltransferase and phospholipase A2 activity in the cell membrane of neutrophils and lymphocytes from patients with Behçet's disease, systemic lupus erythematosus, and rheumatoid arthritis. Clin Chim Acta1988; 174: 1–14.
33.
NiwaYTaniguchiSPhospholipid base exchange in human leukocyte membranes: Quantitation and correlation with other phospholipid biosynthetic pathways. Arch Biochem Biophys1986; 250: 345–357.
34.
HirataFAxelrodJPhospholipid methylation and biological signal transmission. Science1980; 209: 1082–1090.
35.
IshizakaTHirataFIshizakaK Stimulation of phospholipid methylation, Ca2+ influx, and histamine release by bridging of IgE receptors on rat mast cells. Proc Natl Acad Sci USA1980; 77: 1903–1906.
36.
DemlingRHRole of oxygen radicals in acute lung injury. In: Adult Respiratory Distress Syndrome (ArtigasALemaireFSuterPMZapolWM eds). New York: Churchill Livingstone, 1992; pp 121–140.
37.
LamyMDeby-DupontGDebyCMeasurements of mediator cascade during adult respiratory distress syndrome. In: Adult Respiratory Distress Syndrome (ArtigasALemaireFSuterPMZapolWM eds). New York: Churchill Livingstone, 1992: pp 71–88.
