Regulation of CD23 in the chronic inflammatory response in asthma: a role for interferon-gamma and heat shock protein 70 in the TH2 environment.
BACKGROUND
Monocytic cells and alveolar macrophages (AMs) are activated in patients with asthma, producing inflammatory cytokines. This occurs despite a TH2 environment that consists of the cytokines interleukin (IL) 4, IL-10, and IL-13. The mechanism by which this occurs may involve cross-linking of the low-alphaffinity IgE receptor CD23.


OBJECTIVE
To determine the effect of the TH2 environment with interferon-gamma (IFN-gamma) and heat shock protein 70 (HSP 70) on CD23 receptor expression and tumor necrosis factor alpha (TNF-alpha) production.


METHODS
We examined the effect of IL-4 and IL-13 in culture with IFN-gamma and HSP 70 on CD23 expression in both THP-1 cells and AMs from healthy controls via flow cytometry. AMs from mild asthmatic patients and THP-1 cells were evaluated for TNF-alpha production after cross-linking CD23 with immune complexes.


RESULTS
Asthmatic AMs stimulated with anti-IgE exhibited a 5.7- +/- 1.9-fold increase in TNF-alpha protein. AMs from healthy controls increased the geometric mean +/- SD of CD23 2.00- +/- 0.50-fold in IL-4 and 2.14- +/- 0.50-fold in IL-13. THP-1 cells cultured with IL-4 and IL-13 then stimulated with IFN-gamma or HSP 70 increased CD23 expression above baseline as follows: IL-4, 2.16- +/- 0.31-fold; IL-13, 2.66- +/- 0.43-fold; IFN-gamma, 2.03- +/- 0.34-fold; IL-4/IFN-gamma, 9.14- to 4.02-fold; IL-13/IFN-gamma, 11.51- +/- 5.51-fold; IL-4/HSP, 5.20- +/- 0.61-fold; and IL-13/HSP, 5.60- +/- 0.79-fold. Stimulating the CD23 receptor with immune complexes significantly increased TNF-alpha production by THP-1 cells stimulated with IFN-gamma, IL-4, IL-13, or a combination of these.


CONCLUSIONS
Both IFN-gamma and HSP 70, in the TH2 environment, up-regulate CD23 expression and thus may play an important role in maintaining the chronic inflammatory state in asthma.
Harkins
Michelle S
MS
Department of Internal Medicine, University of New Mexico Health Sciences Center, Pulmonary, Allergy & Critical Care Division, Albuquerque Veterans Affairs Medical Center, Albuquerque, New Mexico 87131, USA. mharkins@salud.unm.edu
Moseley
Pope L
PL
Iwamoto
Gary K
GK
D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology*; D018893:Bronchoalveolar Lavage; D002908:Chronic Disease; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D011971:Receptors, Immunologic / Q000378:metabolism; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D018840:HSP70 Heat-Shock Proteins; D007074:Immunoglobulin G; D018793:Interleukin-13; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C026408:anti-IgE antibodies; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma