IgG-, IgA-, and IgE-induced release of leukotriene C4 by monocytes isolated from patients with atopic dermatitis.
Purified peripheral blood monocytes isolated from patients with atopic dermatitis (AD) and from nonallergic normal donors were compared for their abilities to release leukotriene C4 (LTC4), leukotriene B4 (LTB4) and beta-glucuronidase in response to challenge with aggregated immunoglobulins or anti-immunoglobulins. The relationship between mediator release and the number of monocytes that formed rosettes with immunoglobulin-coated indicator cells was examined. Patients with AD had twice as many IgA- and three times as many IgE-rosetting monocytes as normal donors (48 +/- 12% versus 27 +/- 10% and 40 +/- 15% versus 14 +/- 3%, respectively), and yet the amounts of IgA- and IgE-induced LTC4 released were similar for both groups. This apparent discrepancy did not result from a decreased capacity for arachidonate metabolism via the C5-lipoxygenase pathway, since stimulation of monocytes from patients and normal donors with the calcium ionophore A23187 induced similar amounts of LTC4 and LTB4 release (LTC4, 3.0 +/- 1.7 versus 3.0 +/- 1.0 ng/10(6) cells; LTB4, 5.3 +/- 0.7 versus 5.2 +/- 0.5 ng/10(6) cells, respectively). In addition, aggregated IgG-induced LTC4 release by monocytes of both groups was similar, concomitant with an equivalent number of IgG-rosetting cells. Determination of cytophilically bound IgG and IgE by flow cytometry demonstrated that monocytes from atopic patients had more IgG bound than monocytes from normal donors. Similar amounts of IgE were detected on most monocytes from both groups, despite the higher serum IgE levels of patients. However, approximately 3% to 8% of monocytes from atopic but not normal donors stained brightly for IgE, suggesting that relatively large amounts of cytophilic IgE were bound to a small percentage of the patients' monocytes. Challenge of monocytes with anti-IgE or anti-IgG induced release of similar amounts of LTC4 for both groups, despite the presence of more cytophilic IgG on monocytes from atopic donors. These data indicate that monocytes from patients with AD release LTC4 and LTB4 in response to challenge with aggregated IgE or anti-IgE, as well as aggregated IgG, IgA, and anti-IgG. However, under our in vitro conditions, stimulation of patients' monocytes with aggregated IgA or IgE was not associated with increased mediator release, despite higher percentages of IgA- and IgE-rosetting cells compared to normal donors.
Ferreri
N R
NR
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Zeiger
R S
RS
Spiegelberg
H L
HL
D000943:Antigens, Differentiation / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000001:Calcimycin / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G / Q000276:immunology*; D007975:Leukotriene B4 / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D009000:Monocytes / Q000502:physiology*; D011961:Receptors, Fc / Q000032:analysis; D017455:Receptors, IgE; D017452:Receptors, IgG; D012397:Rosette Formation; D013189:SRS-A / Q000378:metabolism*
D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D007070:Immunoglobulin A; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG; D013189:SRS-A; D007975:Leukotriene B4; D007073:Immunoglobulin E; D000001:Calcimycin