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CD48 on blood leukocytes and in serum of asthma patients varies with severity
R S Gangwar1, Y Minai-Fleminger1, M Seaf1
1Pharmacology & Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Background:
CD48 is a membrane receptor (mCD48) on eosinophils and mast cells and exists in a soluble form (sCD48). CD48 has a pivotal role in murine asthma and in the proinflammatory interactions of mast cells with eosinophils via its ligand CD244. Thus, CD48 might be important in human asthma.
Methods:
Therefore, two separate cohorts (IL and UK) comprising mild, moderate, and severe asthma and healthy volunteers were evaluated for blood leukocyte mCD48 expression and sCD48 in serum. Asthmatic bronchial biopsies were immunostained for CD48. sCD48 effect on CD244-dependent eosinophil activation was evaluated.
Results:
Eosinophil mCD48 expression was significantly elevated in moderate while downregulated in severe asthma. mCD48 expression on B, T, and NK cells and monocytes in severe asthma was significantly increased. sCD48 levels were significantly higher in mild while reduced in severe asthma. sCD48 optimal cutoff values for differentiating asthma from health were identified as >1482 pg/ml (IL) and >1619 pg/ml (UK). In asthmatic bronchial biopsies, mCD48 was expressed predominantly by eosinophils. sCD48 inhibited anti-CD244-induced eosinophil activation.
Conclusions:
mCD48 and sCD48 are differentially expressed in the peripheral blood of asthma patients of varying severity. sCD48 inhibits CD244-mediated eosinophil activation. These findings suggest that CD48 may play an important role in human asthma.
Insights
CD48 receptor expression varies in asthma patients, with soluble CD48 (sCD48) inhibiting eosinophil activation. These findings highlight CD48
Area of Science:
- Immunology
- Respiratory Medicine
- Cell Biology
Background:
- CD48, a membrane receptor (mCD48) on eosinophils and mast cells, also exists in a soluble form (sCD48).
- CD48 plays a key role in murine asthma and mast cell-eosinophil interactions via its ligand CD244.
- This suggests a potential role for CD48 in human asthma.
Purpose of the Study:
- To investigate the expression of mCD48 and sCD48 in human asthma.
- To determine the correlation between CD48 expression levels and asthma severity.
- To evaluate the functional impact of sCD48 on eosinophil activation.
Main Methods:
- Analysis of blood leukocyte mCD48 expression and serum sCD48 levels in two cohorts (IL and UK) of mild, moderate, and severe asthma patients and healthy volunteers.
- Immunostaining of asthmatic bronchial biopsies for CD48.
- In vitro evaluation of sCD48's effect on CD244-dependent eosinophil activation.
Main Results:
- Eosinophil mCD48 expression was elevated in moderate and downregulated in severe asthma.
- mCD48 expression increased on B, T, NK cells, and monocytes in severe asthma.
- Serum sCD48 levels were higher in mild but reduced in severe asthma, with specific cutoff values identified for differentiating asthma.
- mCD48 was primarily expressed by eosinophils in asthmatic bronchial biopsies.
- sCD48 inhibited anti-CD244-induced eosinophil activation.
Conclusions:
- Differential expression of mCD48 and sCD48 in the peripheral blood of asthma patients correlates with disease severity.
- sCD48 demonstrates inhibitory effects on CD244-mediated eosinophil activation.
- These findings support a significant role for CD48 in the pathogenesis of human asthma.
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