Histamine release from bronchoalveolar lavage cells from asthmatic subjects after allergen challenge and relationship to the late asthmatic response.
BACKGROUND
Metachromatic cells obtained from asthmatic subjects demonstrate increased spontaneous and stimulated histamine release in vitro. Their ability to synthesize and store proinflammatory cytokines has focused renewed interest on their role in asthma.


OBJECTIVE
The late asthmatic response provides a useful model of clinical asthma. The aim of the study was to examine metachromatic cell derived mediators and histamine releasability in vitro after in vivo allergen exposure in atopic subjects with and without asthma and relate them to the type of physiological response observed.


METHODS
Bronchoalveolar lavage (BAL) cells were obtained 4 h after challenge from asthmatics exhibiting a single early response (EAR, n = 5), a dual response (LAR, n = 7), unchallenged (basal, n = 5), atopic non-asthmatic (ANA, n = 6) and non-atopic non-asthmatics (normal, n = 5). BAL histamine and tryptase concentrations and in vitro histamine release (HR) after stimulation with anti-IgE, allergen, A23187, conconavalin A and substance P were compared.


RESULTS
Metachromatic cell numbers were lower in normal controls compared with all asthmatic groups and in LAR compared with EAR. Metachromatic cell derived mediators were higher in asthmatic compared with normal subjects. Spontaneous HR in LAR (20.5 +/- 5.0%) was lower than EAR (29.5 +/- 3.9%) and ANA (30.2 +/- 1.4%) (P < 0.05). No differences were seen in stimulated HR between EAR and LAR. HR in ANA stimulated with anti-IgE was greater than LAR (P < 0.05). HR in ANA stimulated with anti-IgE was greater than LAR (P < 0.05). After stimulation with ionophore A23187 (1 microM), release was greater in LAR compared with basal (P < 0.05) and no different at 5 microM. All subject groups responded to substance P (SP) but was significantly more in the asthmatic subjects compared to normal controls (P < 0.05). Allergen challenge did not modify the response of asthmatic subjects to SP.


CONCLUSIONS
Functional differences in metachromatic cell reactivity are present in atopic subjects 4h after in vivo allergen exposure which relate to the physiological response observed after this time and suggest that there is ongoing metachromatic cell degranulation subjects who subsequently develop LAR.
Heaney
L G
LG
Department of Respiratory Medicine, Royal Victoria Hospital, UK.
Cross
L J
LJ
Ennis
M
M
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology* / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001249:Asthma / Q000276:immunology*; D001491:Basophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D053818:Chymases; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006636:Histamine Release / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000493:pharmacokinetics; D007958:Leukocyte Count; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012697:Serine Endopeptidases / Q000493:pharmacokinetics; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors; D053802:Tryptases
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D018836:Inflammation Mediators; C026408:anti-IgE antibodies; D003208:Concanavalin A; D013373:Substance P; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases