Activation of tracheal smooth muscle responsiveness by fMLP-treated HL-60 cells and neutrophils.
We assessed the effects of cultured human promyelocytic leukemia (HL-60) cells and polymorphonuclear leukocytes (neutrophils) isolated from peripheral human blood on tracheal smooth muscle responsiveness in 40 male Hartley guinea pigs. Undifferentiated HL-60 cells (16-25 passages) were activated in vitro by incubation with 1 microM f-Met-Leu-Phe (fMLP), and force of contraction was measured isometrically using an in situ preparation of tracheal smooth muscle. Increasing concentrations of acetylcholine (ACh; 10(-10) to 10(-6) mol/cm2 tracheal surface) were applied topically to the epithelial surface pretreated with 4 x 10(6) fMLP-activated HL-60 cells, 4 x 10(6) fMLP-activated neutrophils, 4 x 10(6) sham-activated HL-60 cells, fMLP+vehicle, or vehicle control. Topical application of fMLP-activated HL-60 cells caused a maximum active tension (AT) of 1.13 +/- 0.2 g/cm after 5 min; fMLP-activated neutrophils, sham-activated HL-60 cells, or fMLP+vehicle had no effect. The fMLP-activated HL-60 cells also caused substantial augmentation of tracheal contraction to ACh (P < 0.05 vs. sham-activated cells for all concentrations > 10(-9) mol/cm2). Although fMLP treatment caused 247 +/- 28% increase from baseline level in O2-. production, neither direct contraction nor augmentation of muscarinic stimulation was demonstrated after topical application of 4 x 10(6) neutrophils. In 12 other preparations, fMLP-activated HL-60 cells were pretreated with either 10 microM indomethacin (Indo) or 100 microM A63162, a 5-lipoxygenase inhibitor. Pretreatment with Indo caused complete blockade of direct tracheal contraction and 88 +/- 13% blockade of muscarinic augmentation; there was no effect after A63162.(ABSTRACT TRUNCATED AT 250 WORDS)
Munoz
N M
NM
Department of Medicine, University of Chicago, Illinois 60637.
Hamann
K J
KJ
Vita
A
A
Cozzi
P J
PJ
Baranowski
S
S
Solway
J
J
Leff
A R
AR
D000081:Acetamides / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology* / Q000503:physiopathology*; D008084:Lipoxygenase / Q000378:metabolism / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010647:Phenyl Ethers; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology; D014132:Trachea / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000081:Acetamides; D016859:Lipoxygenase Inhibitors; D010647:Phenyl Ethers; C068663:N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D007213:Indomethacin