Identification of T lymphocytes, Macrophages, and Activated Eosinophils in the Bronchial Mucosa in Intrinsic Asthma: Relationship to Symptoms and Bronchial Responsiveness

Abstract

Using immunohistochemistry and a panel of monoclonal antibodies, we have compared T-lymphocyte, eosinophil, macrophage, and neutrophil infiltration in bronchial biopsies from 10 intrinsic (nonallergic) asthmatics (IA) and seven extrinsic (allergic) asthmatic (EA), with similar degrees of disease severity. The results were compared with 12 normal healthy nonatopic controls (NC). All subjects were nonsmokers and were not taking oral or inhaled corticosteroids. An intense mononuclear cell infiltrate was identified in IA with an increase in the number of CD45+ cells (total leukocytes), CD3+ and CD4+ lymphocytes, and CD68+ macrophages (p < 0.03, p < 0.01, p < 0.03, and p < 0.03, respectively), compared with NC. Increases were also found in CD4+ (p < 0.05) and CD68+ (p < 0.05) cell numbers between IA and EA. IL-2 receptor-bearing cells (CD25+) and the number of total (MBP+) and actively secreting (EG2+) eosinophils, were also increased in IA compared with NC (p < 0.01, p < 0.01, and p < 0.01, respectively). Similar increases in EG2+ eosinophils and CD25+ (IL-2 receptor-positive) cells were observed in EA (p < 0.01 and p < 0.02, respectively). No differences were detected in the three groups for the number of elastase-positive cells (neutrophils). EG2+ numbers in IA correlated with the Aas asthma symptoms score (r = 0.65, p < 0.05), whereas EG2+ cell numbers in all asthmatics (IA + EA) correlated with airway methacholine responsiveness (r = -0.55, p < 0.03) and with the Aas asthma symptom score (r = 0.54, p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Segmental Bronchial Provocation Induces Nasal Inflammation in Allergic Rhinitis Patients

“…Several investigators have shown that eosinophilic inflammation of the airways is correlated with the severity of asthma (6,29). In our study, we also found a strong correlation of clinical data (FEV 1 and VAS score) with inflammatory parameters (eosinophils and IL-5 expression) in allergic lower airways, but were unable to demonstrate any correlation between clinical parameters and inflammatory cell numbers in the nose.…”

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

“…Increased numbers of polymorphonuclear cells (mainly eosinophils) and mononuclear cells (mainly lymphocytes) have been identified at autopsy in the airways of patients dying of asthma [1][2][3] and in patients with less severe asthma, by use of bronchoalveolar lavage (BAL) [4][5][6][7] and biopsy of proximal airways [7][8][9][10][11][12][13][14][15]. Immunohistochemical techniques have identified the CD4+ subset of T-lymphocytes in the airways of patients with asthma, and have demonstrated that these lymphocytes and eosinophils express markers of functional activation to a greater extent than those from nonasthmatic subjects [11,12,15,16].…”

“…Immunohistochemical techniques have identified the CD4+ subset of T-lymphocytes in the airways of patients with asthma, and have demonstrated that these lymphocytes and eosinophils express markers of functional activation to a greater extent than those from nonasthmatic subjects [11,12,15,16].…”

Interleukin-4 and interleukin-5 as targets for the inhibition of eosinophilic inflammation and allergic airways hyperreactivity

“…There is accumulating evidence from clinical investigations and animal models of allergic airways inflammation that CD4 + Th 2 type lymphocytes and eosinophils play a critical role in both the induction and pathogenesis of asthma (Bradley et al1991, Walker et al 1992a,b, Foster et al 1996. A number of investigations have shown a correlation between the accumulation of activated CD4 + T-cells and eosinophils, their inflammatory products in the lung and disease severity (De Monchy et al 1985, Fukuda et al 1985, Wardlaw et al 1988, Beasley et al 1989, Frick et al 1989, Azzawi et al 1990, Bousquet et al 1990, Broide et al 1991, Walker et al 1991a,b, Bentley et al 1992, Ohashi et al 1992.…”

“…While the chain of events leading to asthma involves a complex cascade of interacting cells and inflammatory mediators, it is becoming apparent that the cytokines interleukin (IL)-4 (IL-4) and IL-5 secreted from allergen-specific CD4 + Th 2 type cells play central roles in initiating and sustaining an asthmatic response by regulating the recruitment and/or activation of airways mast cells and eosinophils (Wierenga et al 1990, Walker et al 1991a,b, Robinson et al 1992. Increased levels of IL-4 and IL-5 are found in the respiratory secretions from atopic asthmatics (Walker et al 1991a,b).…”