Systemic inhibition of the angiotensin-converting enzyme limits lipopolysaccharide-induced lung neutrophil recruitment through both bradykinin and angiotensin II-regulated pathways

被引:38
作者
Arndt, Patrick G.
Young, Scott K.
Poch, Katie R.
Nick, Jerry A.
Falk, Sandor
Schrier, Robert W.
Worthen, G. Scott
机构
[1] Univ Colorado, Hlth Sci Ctr, Div Pulm & Crit Care Med, Denver, CO 80206 USA
[2] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO USA
[3] Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Denver, CO 80206 USA
关键词
D O I
10.4049/jimmunol.177.10.7233
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Recruitment of neutrophils to the lung is a sentinel event in acute lung inflammation. Identifying mechanisms that regulate neutrophil recruitment to the lung may result in strategies to limit lung damage and improve clinical outcomes. Recently, the renin angiotensin system (RAS) has been shown to regulate neutrophil influx in acute inflammatory models of cardiac, neurologic, and gastrointestinal disease. As a role for the RAS in LPS-induced acute lung inflammation has not been described, we undertook this study to examine the possibility that the RAS regulates neutrophil recruitment to the lung after LPS exposure. Pretreatment of mice with the angiotensin-converting enzyme (ACE) inhibitor enalapril, but not the anti-hypertensive hydralazine, decreased pulmonary neutrophil recruitment after exposure to LPS. We hypothesize that inhibition of LPS-induced neutrophil accumulation to the lung with enalapril occurred through both an increase in bradykinin, and a decrease in angiotensin II (ATII), mediated signaling. Bradykinin receptor blockade reversed the inhibitory effect of enalapril on neutrophil recruitment. Similarly, pretreatment with bradykinin receptor agonists inhibited IL-8-induced neutrophil chemotaxis and LPS-induced neutrophil recruitment to the lung. Inhibition of ATII-mediated signaling, with the ATII receptor la inhibitor losartan, decreased LPS-induced pulmonary neutrophil recruitment, and this was suggested to occur through decreased PAI-1 levels. LPS-induced PAI-1 levels were diminished in animals pretreated with losartan and in those deficient for the ATII receptor 1a. Taken together, these results suggest that ACE regulates LPS-induced pulmonary neutrophil recruitment via modulation of both bradykinin- and ATII-mediated pathways, each regulating neutrophil recruitment by separate, but distinct, mechanisms.
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页码:7233 / 7241
页数:9
相关论文
共 65 条
  • [51] BENEFICIAL-EFFECTS OR A BRADYKININ ANTAGONIST IN A MODEL OF GRAM-NEGATIVE SEPSIS
    RIDINGS, PC
    BLOCHER, CR
    FISHER, BJ
    FOWLER, AA
    SUGERMAN, HJ
    [J]. JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, 1995, 39 (01) : 81 - 89
  • [52] STIMULATION OF PLASMINOGEN-ACTIVATOR INHIBITOR INVIVO BY INFUSION OF ANGIOTENSIN-II - EVIDENCE OF A POTENTIAL INTERACTION BETWEEN THE RENIN-ANGIOTENSIN SYSTEM AND FIBRINOLYTIC FUNCTION
    RIDKER, PM
    GABOURY, CL
    CONLIN, PR
    SEELY, EW
    WILLIAMS, GH
    VAUGHAN, DE
    [J]. CIRCULATION, 1993, 87 (06) : 1969 - 1973
  • [53] MODULATION OF ENDOTOXIN-INDUCED NEUTROPHIL ALVEOLITIS BY CAPTOPRIL AND BY HYPEROXIA
    RINALDO, JE
    DAUBER, JH
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1985, 37 (01) : 87 - 99
  • [54] Blocking of endogenous nitric oxide increases white blood cell accumulation in rat lung
    Roman, A
    LeGallo, R
    McGahren, ED
    [J]. JOURNAL OF PEDIATRIC SURGERY, 2004, 39 (01) : 48 - 52
  • [55] Sato E, 1996, J IMMUNOL, V157, P3122
  • [56] ASSOCIATION BETWEEN A DELETION POLYMORPHISM OF THE ANGIOTENSIN-CONVERTING-ENZYME GENE AND LEFT-VENTRICULAR HYPERTROPHY
    SCHUNKERT, H
    HENSE, HW
    HOLMER, SR
    STENDER, M
    PERZ, S
    KEIL, U
    LORELL, BH
    RIEGGER, GAJ
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1994, 330 (23) : 1634 - 1638
  • [57] ACE inhibitors and pneumonia
    Sekizawa, K
    Matsui, T
    Nakagawa, T
    Nakayama, K
    Sasaki, H
    [J]. LANCET, 1998, 352 (9133) : 1069 - 1069
  • [58] Role of the bradykinin B2 receptor for the local and systemic inflammatory response that follows severe reperfusion injury
    Souza, DG
    Pinho, V
    Pesquero, JL
    Lomez, ES
    Poole, S
    Juliano, L
    Correa, A
    Castro, MSD
    Teixeira, MM
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2003, 139 (01) : 129 - 139
  • [59] BRONCHOALVEOLAR LAVAGE FLUID ANGIOTENSIN-CONVERTING ENZYME IN INTERSTITIAL LUNG-DISEASES
    SPECKS, U
    MARTIN, WJ
    ROHRBACH, MS
    [J]. AMERICAN REVIEW OF RESPIRATORY DISEASE, 1990, 141 (01): : 117 - 123
  • [60] Regulatory effects of NOS on acute lung inflammatory responses in mice
    Speyer, CL
    Neff, TA
    Warner, RL
    Guo, RF
    Sarma, JV
    Riedemann, NC
    Murphy, ME
    Murphy, HS
    Ward, PA
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (06) : 2319 - 2328