Neutrophil-induced human bronchial hyperresponsiveness in vitro--pharmacological modulation.
Although it has been postulated that inflammatory cells cause the bronchial hyperresponsiveness which is diagnostic of asthma, until recently there has been little direct evidence of such a link. We have recently shown that calcium ionophore-activated human neutrophils and eosinophils can induce a state of human airway hyperresponsiveness in vitro. In this study we have shown that the anti-inflammatory agent nedocromil sodium, 10(-7) M, inhibited the hyperresponsiveness induced by products released from ionophore activated neutrophils but did not inhibit the release of leukotriene B4 from the same cells. Neutrophil-induced bronchial hyperresponsiveness was also inhibited by pre-treatment of the bronchial tissues with a thromboxane A2 and prostaglandin receptor antagonist, GR32191, 10(-7) M. These findings indicate that cyclooxygenase products are involved in bronchial hyperresponsiveness induced by inflammatory cell products in vitro and that their release can be inhibited by nedocromil sodium.
Department of Pharmacy, University of Sydney, New South Wales, Australia.
J M
JM
Hughes
K O
KO
McKay
P R
PR
Johnson
S
S
Tragoulias
J L
JL
Black
C L
CL
Armour
D001713:Biphenyl Compounds / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D016535:Bronchial Hyperreactivity / Q000473:pathology*; D000001:Calcimycin / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D017835:Nedocromil; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D015363:Quinolones / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D015363:Quinolones; D017482:Receptors, Thromboxane; D017835:Nedocromil; D007975:Leukotriene B4; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C060013:vapiprost