Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics

Cellular, mediator, and permeability changes

Mark Chang Hwa Liu, W. C. Hubbard, D. Proud, B. A. Stealey, S. J. Galli, A. Kagey-Sobotka, E. R. Bleecker, L. M. Lichtenstein

Research output: Contribution to journalArticle

Abstract

Asthma may represent the clinical manifestations of a unique form of chronic airway inflammation and is often associated with allergy. To better define the components of allergic inflammation in the lung, fluids obtained by bronchoalveolar lavage (BAL) were examined for cells, inflammatory mediators, and markers of airway permeability 5 min and 19 h following instillation of ragweed antigen directly into an airway segment of allergic asthmatic subjects. The 5-min response to antigen challenge (n = 10) was characterized by 17- to 208-fold increases in histamine, prostaglandin D2 (PGD2), and its metabolite, 9α,11β-PGF2, thromboxane B2, and 6-keto-PGF(1α) compared with a saline-challenged segment (0.004 <p <0.017). The increases in most of these mediators were significantly correlated with each other (0.0001 <p ≤ 0.01), and the magnitude of all significant mediator increases was directly correlated with skin test sensitivity to ragweed antigen (0.007 ≤ p ≤ 0.05). There was also a slight increase in kinins (p = 0.04). Changes in cells and airway permeability were not detected. In contrast, the 19-h response to antigen challenge (n = 9) was characterized by a 13-fold increase in total cells recovered by BAL. Eosinophils, basophils, and lymphocytes were significantly increased and comprised 38, 1, and 9% of total cells, respectively. A neutrophil influx was also observed but was not specific for antigen challenge since a similar change was observed in a sham, saline-challenged site. Histamine and PGD2 remained elevated in the 19-h response (p <0.05), but levels were much lower than in the 5-min response. The profile of other prostanoid mediators was also reversed in the 19-h versus 5-min response, with only PGE2 and PGF(2α) increased in the later response (p <0.05). Albumin and urea, used as markers of airway permeability, were increased 20- and 6-fold, respectively (p <0.05). Kinins increased 8-fold (p <0.01). As in the 5-min response, skin test sensitivity was directly correlated with certain mediator (histamine, PGD2, PGE2, PGF(2α), and kinins) and cellular changes (eosinophils) in the 19-h response to antigen (0.01 <p <0.05). These findings demonstrate that allergic inflammation in the lung is initiated by the release of multiple inflammatory mediators dominated by products derived from mast cells. However, the profile of released mediators suggests the early involvement of many other cell types in the immediate response. Subsequent inflammatory changes include the continued production of mediators, exudation of plasma proteins, and the recruitment of inflammatory cells, particularly eosinophils, basophils, and lymphocytes. Since many of these changes are characteristic of asthma, these findings support a role for allergic inflammation in the pathogenesis of this disease.

Original languageEnglish (US)
Pages (from-to)51-58
Number of pages8
JournalAmerican Review of Respiratory Disease
Volume144
Issue number1
StatePublished - 1991

Fingerprint

Ambrosia
Permeability
Antigens
Prostaglandin D2
Kinins
Prostaglandins F
Eosinophils
Histamine
Basophils
Skin Tests
Dinoprostone
Pneumonia
Asthma
Lymphocytes
Inflammation
Thromboxane B2
Dinoprost
Bronchoalveolar Lavage Fluid
Bronchoalveolar Lavage
Mast Cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics : Cellular, mediator, and permeability changes. / Liu, Mark Chang Hwa; Hubbard, W. C.; Proud, D.; Stealey, B. A.; Galli, S. J.; Kagey-Sobotka, A.; Bleecker, E. R.; Lichtenstein, L. M.

In: American Review of Respiratory Disease, Vol. 144, No. 1, 1991, p. 51-58.

Research output: Contribution to journalArticle

Liu, Mark Chang Hwa ; Hubbard, W. C. ; Proud, D. ; Stealey, B. A. ; Galli, S. J. ; Kagey-Sobotka, A. ; Bleecker, E. R. ; Lichtenstein, L. M. / Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics : Cellular, mediator, and permeability changes. In: American Review of Respiratory Disease. 1991 ; Vol. 144, No. 1. pp. 51-58.
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