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.
Hughes
J M
JM
Department of Pharmacy, University of Sydney, New South Wales, Australia.
McKay
K O
KO
Johnson
P R
PR
Tragoulias
S
S
Black
J L
JL
Armour
C L
CL
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