Goblet cell degranulation after antigen challenge in sensitized guinea pigs. Role of neutrophils.
Mucus hypersecretion is a common characteristic of asthma. Acute severe asthma is often associated with neutrophilic infiltration into airways. Neutrophils contain elastase, a potent secretagogue in airways. Therefore, we hypothesized that instillation of ovalbumin in sensitized guinea pigs causes goblet cell secretion by releasing elastase from recruited neutrophils. When we instilled ovalbumin into the trachea of ovalbumin-sensitized guinea pigs, early recruitment of neutrophils identified by 3,3'- diaminobenzidine staining, and goblet cell degranulation measured with a semiautomatic computer-based imaging system occurred. The Leumedin NPC 15669 (a drug that inhibits leukocyte recruitment) and an antibody to intercellular adhesion molecule-1 (ICAM-1) both prevented neutrophil recruitment and goblet cell degranulation, implicating leukocytes in the response. Using immunofluorescence we showed that the leukocytes recruited early after antigen challenge were CD-16-positive, implicating neutrophils. Pretreatment with the selective neutrophil elastase inhibitor ICI 200,355 also prevented ovalbumin-induced goblet cell degranulation, implicating elastase. We conclude that ovalbumin-induced goblet cell degranulation is due to neutrophil recruitment and elastase release.
Cardiovascular Research Institute and Department of Medicine, University of California San Francisco, San Francisco, California, USA.
C
C
Agusti
K
K
Takeyama
L O
LO
Cardell
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I
Ueki
J
J
Lausier
Y P
YP
Lou
J A
JA
Nadel
D015100:3,3'-Diaminobenzidine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001249:Asthma / Q000473:pathology / Q000503:physiopathology; D015550:Cell Degranulation / Q000276:immunology; D002465:Cell Movement; D004396:Coloring Agents; D019084:Fluorescent Antibody Technique, Indirect; D020397:Goblet Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006168:Guinea Pigs; D007091:Image Processing, Computer-Assisted; D007114:Immunization; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D009093:Mucus / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D017452:Receptors, IgG / Q000032:analysis; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014132:Trachea / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D000941:Antigens; D004396:Coloring Agents; D009842:Oligopeptides; D017452:Receptors, IgG; D015842:Serine Proteinase Inhibitors; C069366:ICI 200355; D018799:Intercellular Adhesion Molecule-1; C071244:N-(9H-(2,7-dimethylfluoren-9-ylmethoxy)carbonyl)leucine; D015100:3,3'-Diaminobenzidine; D010047:Ovalbumin; D019272:Leukocyte Elastase; D007930:Leucine